Pesticidal compositions and processes related thereto

ABSTRACT

This document discloses molecules having the following formula (“Formula One”): 
     
       
         
         
             
             
         
       
     
     and processes associated therewith.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional PatentApplication Ser. No. 61/739,045 filed Dec. 19, 2012, the entiredisclosure of which is hereby expressly incorporated by reference.

FIELD OF THE DISCLOSURE

The invention disclosed in this document is related to the field ofprocesses to produce molecules that are useful as pesticides (e.g.,acaricides, insecticides, molluscicides, and nematicides), suchmolecules, and processes of using such molecules to control pests.

BACKGROUND OF THE DISCLOSURE

Pests cause millions of human deaths around the world each year.Furthermore, there are more than ten thousand species of pests thatcause losses in agriculture. The world-wide agricultural losses amountto billions of U.S. dollars each year.

Termites cause damage to all kinds of private and public structures. Theworld-wide termite damage losses amount to billions of U.S. dollars eachyear.

Stored food pests eat and adulterate stored food. The world-wide storedfood losses amount to billions of U.S. dollars each year, but moreimportantly, deprive people of needed food.

There is an acute need for new pesticides. Certain pests are developingresistance to pesticides in current use. Hundreds of pest species areresistant to one or more pesticides. The development of resistance tosome of the older pesticides, such as DDT, the carbamates, and theorganophosphates, is well known. But resistance has even developed tosome of the newer pesticides, for example, imidacloprid.

Therefore, for many reasons, including the above reasons, a need existsfor new pesticides.

DEFINITIONS

The examples given in the definitions are generally non-exhaustive andmust not be construed as limiting the invention disclosed in thisdocument. It is understood that a substituent should comply withchemical bonding rules and steric compatibility constraints in relationto the particular molecule to which it is attached.

“Alkenyl” means an acyclic, unsaturated (at least one carbon-carbondouble bond), branched or unbranched, substituent consisting of carbonand hydrogen, for example, vinyl, allyl, butenyl, pentenyl, and hexenyl.

“Alkenyloxy” means an alkenyl further consisting of a carbon-oxygensingle bond, for example, allyloxy, butenyloxy, pentenyloxy, hexenyloxy.

“Alkoxy” means an alkyl further consisting of a carbon-oxygen singlebond, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy,isobutoxy, and tert-butoxy.

“Alkyl” means an acyclic, saturated, branched or unbranched, substituentconsisting of carbon and hydrogen, for example, methyl, ethyl, (C₃)alkylwhich represents n-propyl and isopropyl), (C₄)alkyl which representsn-butyl, sec-butyl, isobutyl, and tert-butyl.

“Alkynyl” means an acyclic, unsaturated (at least one carbon-carbontriple bond), branched or unbranched, substituent consisting of carbonand hydrogen, for example, ethynyl, propargyl, butynyl, and pentynyl.

“Alkynyloxy” means an alkynyl further consisting of a carbon-oxygensingle bond, for example, pentynyloxy, hexynyloxy, heptynyloxy, andoctynyloxy.

“Aryl” means a cyclic, aromatic substituent consisting of hydrogen andcarbon, for example, phenyl, naphthyl, and biphenyl.

“(C_(x)-C_(y))” where the subscripts “x” and “y” are integers such as 1,2, or 3, means the range of carbon atoms for a substituent—for example,(C₁-C₄)alkyl means methyl, ethyl, n-propyl, isopropyl, n-butyl,sec-butyl, isobutyl, and tert-butyl, each individually.

“Cycloalkenyl” means a monocyclic or polycyclic, unsaturated (at leastone carbon-carbon double bond) substituent consisting of carbon andhydrogen, for example, cyclobutenyl, cyclopentenyl, cyclohexenyl,norbornenyl, bicyclo[2.2.2]octenyl, tetrahydronaphthyl,hexahydronaphthyl, and octahydronaphthyl.

“Cycloalkenyloxy” means a cycloalkenyl further consisting of acarbon-oxygen single bond, for example, cyclobutenyloxy,cyclopentenyloxy, norbornenyloxy, and bicyclo[2.2.2]octenyloxy.

“Cycloalkyl” means a monocyclic or polycyclic, saturated substituentconsisting of carbon and hydrogen, for example, cyclopropyl, cyclobutyl,cyclopentyl, norbornyl, bicyclo[2.2.2]octyl, and decahydronaphthyl.

“Cycloalkoxy” means a cycloalkyl further consisting of a carbon-oxygensingle bond, for example, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy,norbornyloxy, and bicyclo[2.2.2]octyloxy.

“Halo” means fluoro, chloro, bromo, and iodo.

“Haloalkoxy” means an alkoxy further consisting of, from one to themaximum possible number of identical or different, halos, for example,fluoromethoxy, trifluoromethoxy, 2,2-difluoropropoxy, chloromethoxy,trichloromethoxy, 1,1,2,2-tetrafluoroethoxy, and pentafluoroethoxy.

“Haloalkyl” means an alkyl further consisting of, from one to themaximum possible number of, identical or different, halos, for example,fluoromethyl, trifluoromethyl, 2,2-difluoropropyl, chloromethyl,trichloromethyl, and 1,1,2,2-tetrafluoroethyl.

“Heterocyclyl” means a cyclic substituent that may be fully saturated,partially unsaturated, or fully unsaturated, where the cyclic structurecontains at least one carbon and at least one heteroatom, where saidheteroatom is nitrogen, sulfur, or oxygen. In the case of sulfur, thatatom can be in other oxidation states such as a sulfoxide and sulfone.Examples of aromatic heterocyclyls include, but are not limited to,benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl,benzothienyl, benzothiazolyl, cinnolinyl, furanyl, imidazolyl,indazolyl, indolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl,oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl,pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl,quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl,triazinyl, and triazolyl. Examples of fully saturated heterocyclylsinclude, but are not limited to, piperazinyl, piperidinyl, morpholinyl,pyrrolidinyl, oxetanyl, tetrahydrofuranyl, tetrahydrothienyl andtetrahydropyranyl. Examples of partially unsaturated heterocyclylsinclude, but are not limited to, 1,2,3,4-tetrahydroquinolinyl,4,5-dihydro-oxazolyl, 4,5-dihydro-1H-pyrazolyl, 4,5-dihydro-isoxazolyl,and 2,3-dihydro-[1,3,4]-oxadiazolyl.

Additional examples include the following

DETAILED DESCRIPTION OF THE DISCLOSURE

This document discloses molecules having the following formula (“FormulaOne”):

wherein:

(a) R1 is selected from

-   -   (1) H, F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl,        (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy, S(C₁-C₈)alkyl,        S(halo(C₁-C₈)alkyl), S(O)(C₁-C₈)alkyl, S(O)(halo(C₁-C₈)alkyl),        S(O)₂(C₁-C₈)alkyl, S(O)₂(halo(C₁-C₈)alkyl), N(R14)(R15),    -   (2) substituted (C₁-C₈)alkyl, wherein said substituted        (C₁-C₈)alkyl has one or more substituents selected from CN and        NO₂,    -   (3) substituted halo(C₁-C₈)alkyl, wherein said substituted        halo(C₁-C₈)alkyl, has one or more substituents selected from CN        and NO₂,    -   (4) substituted (C₁-C₈)alkoxy, wherein said substituted        (C₁-C₈)alkoxy has one or more substituents selected from CN and        NO₂, and    -   (5) substituted halo(C₁-C₈)alkoxy, wherein said substituted        halo(C₁-C₈)alkoxy has one or more substituents selected from CN        and NO₂;

(b) R2 is selected from

-   -   (1) H, F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl,        (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy, S(C₁-C₈)alkyl,        S(halo(C₁-C₈)alkyl), S(O)(C₁-C₈)alkyl, S(O)(halo(C₁-C₈)alkyl),        S(O)₂(C₁-C₈)alkyl, S(O)₂(halo(C₁-C₈)alkyl), N(R14)(R15),    -   (2) substituted (C₁-C₈)alkyl, wherein said substituted        (C₁-C₈)alkyl has one or more substituents selected from CN and        NO₂,    -   (3) substituted halo(C₁-C₈)alkyl, wherein said substituted        halo(C₁-C₈)alkyl, has one or more substituents selected from CN        and NO₂,    -   (4) substituted (C₁-C₈)alkoxy, wherein said substituted        (C₁-C₈)alkoxy has one or more substituents selected from CN and        NO₂, and    -   (5) substituted halo(C₁-C₈)alkoxy, wherein said substituted        halo(C₁-C₈)alkoxy has one or more substituents selected from CN        and NO₂;

(c) R3 is selected from

-   -   (1) H, F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl,        (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy, S(C₁-C₈)alkyl,        S(halo(C₁-C₈)alkyl), S(O)(C₁-C₈)alkyl, S(O)(halo(C₁-C₈)alkyl),        S(O)₂(C₁-C₈)alkyl, S(O)₂(halo(C₁-C₈)alkyl), N(R14)(R15),    -   (2) substituted (C₁-C₈)alkyl, wherein said substituted        (C₁-C₈)alkyl has one or more substituents selected from CN and        NO₂,    -   (3) substituted halo(C₁-C₈)alkyl, wherein said substituted        halo(C₁-C₈)alkyl, has one or more substituents selected from CN        and NO₂,    -   (4) substituted (C₁-C₈)alkoxy, wherein said substituted        (C₁-C₈)alkoxy has one or more substituents selected from CN and        NO₂, and    -   (5) substituted halo(C₁-C₈)alkoxy, wherein said substituted        halo(C₁-C₈)alkoxy has one or more substituents selected from CN        and NO₂;

(d) R4 is selected from

-   -   (1) H, F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl,        (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy, S(C₁-C₈)alkyl,        S(halo(C₁-C₈)alkyl), S(O)(C₁-C₈)alkyl, S(O)(halo(C₁-C₈)alkyl),        S(O)₂(C₁-C₈)alkyl, S(O)₂(halo(C₁-C₈)alkyl), N(R14)(R15),    -   (2) substituted (C₁-C₈)alkyl, wherein said substituted        (C₁-C₈)alkyl has one or more substituents selected from CN and        NO₂,    -   (3) substituted halo(C₁-C₈)alkyl, wherein said substituted        halo(C₁-C₈)alkyl, has one or more substituents selected from CN        and NO₂,    -   (4) substituted (C₁-C₈)alkoxy, wherein said substituted        (C₁-C₈)alkoxy has one or more substituents selected from CN and        NO₂, and    -   (5) substituted halo(C₁-C₈)alkoxy, wherein said substituted        halo(C₁-C₈)alkoxy has one or more substituents selected from CN        and NO₂;

(e) R5 is selected from

-   -   (1) H, F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl,        (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy, S(C₁-C₈)alkyl,        S(halo(C₁-C₈)alkyl), S(O)(C₁-C₈)alkyl, S(O)(halo(C₁-C₈)alkyl),        S(O)₂(C₁-C₈)alkyl, S(O)₂(halo(C₁-C₈)alkyl), N(R14)(R15),    -   (2) substituted (C₁-C₈)alkyl, wherein said substituted        (C₁-C₈)alkyl has one or more substituents selected from CN and        NO₂,    -   (3) substituted halo(C₁-C₈)alkyl, wherein said substituted        halo(C₁-C₈)alkyl, has one or more substituents selected from CN        and NO₂,    -   (4) substituted (C₁-C₈)alkoxy, wherein said substituted        (C₁-C₈)alkoxy has one or more substituents selected from CN and        NO₂, and    -   (5) substituted halo(C₁-C₈)alkoxy, wherein said substituted        halo(C₁-C₈)alkoxy has one or more substituents selected from CN        and NO₂;

(f) R6 is a (C₁-C₈)haloalkyl;

(g) R7 is selected from H, F, Cl, Br, I, OH, (C₁-C₈)alkoxy, andhalo(C₁-C₈)alkoxy;

(h) R8 is selected from H, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl, OR14, andN(R14)(R15);

(i) R9 is selected from H, F, Cl, Br, I, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl,(C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy, OR14, and N(R14)(R15);

(j) R10 is selected from

-   -   (1) H, F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl,        (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy, cyclo(C₃-C₆)alkyl,        S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), S(O)(C₁-C₈)alkyl,        S(O)(halo(C₁-C₈)alkyl), S(O)₂(C₁-C₈)alkyl,        S(O)₂(halo(C₁-C₈)alkyl), NR14R15, C(═O)H, C(═O)N(R14)(R15),        CN(R14)(R15)(═NOH), (C═O)O(C₁-C₈)alkyl, (C═O)OH, heterocyclyl,        (C₂-C₈)alkenyl, halo(C₂-C₈)alkenyl, (C₂-C₈)alkynyl,    -   (2) substituted (C₁-C₈)alkyl, wherein said substituted        (C₁-C₈)alkyl has one or more substituents selected from OH,        (C₁-C₈)alkoxy, S(C₁-C₈)alkyl, S(O)(C₁-C₈)alkyl,        S(O)₂(C₁-C₈)alkyl, NR14R15, and    -   (3) substituted halo(C₁-C₈)alkyl, wherein said substituted        halo(C₁-C₈)alkyl, has one or more substituents selected from        (C₁-C₈)alkoxy, S(C₁-C₈)alkyl, S(O)(C₁-C₈)alkyl,        S(O)₂(C₁-C₈)alkyl, and N(R14)(R15);

(k) R11 is C(═X5)N(H)((C₀-C₈)alkyl)N(R11a)(C(═X5)N(H)(R11b))

-   -   wherein each X5 is independently selected from O or S, and    -   wherein each R11a is independently selected from H,        (C₁-C₈)alkyl, substituted (C₁-C₈)alkyl, halo(C₁-C₈)alkyl,        substituted halo(C₁-C₈)alkyl, cyclo(C₃-C₈)alkyl, substituted        cyclo(C₃-C₈)alkyl,    -   wherein each said substituted (C₁-C₈)alkyl has one or more        substituents selected from F, Cl, Br, I, CN, NO₂, OC(═O)H, OH,        S(C₁-C₈)alkyl, S(O)(C₁-C₈)alkyl, S(O)₂(C₁-C₈)alkyl, OS(O)₂aryl,        N((C₁-C₈)alkyl)₂ (wherein each (C₁-C₈)alkyl is independently        selected), aryl, substituted aryl, heterocyclyl, substituted        heterocyclyl, wherein each said substituted aryl has one or more        substituents selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,        halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,        S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈)alkyl)₂ (wherein        each (C₁-C₈)alkyl is independently selected), and oxo, wherein        each said substituted heterocyclyl has one or more substituents        selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,        halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,        S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈)alkyl)₂ (wherein        each (C₁-C₈)alkyl is independently selected), C(═O)(C₁-C₈)alkyl,        C(═O)(C₃-C₆)cycloalkyl, S(═O)₂(C₁-C₈)alkyl, NR14R15, and oxo,        wherein each said substituted-aryl has one or more substituents        selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,        halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,        S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈)alkyl)₂ (wherein        each (C₁-C₈)alkyl is independently selected), and oxo,    -   wherein said substituted halo(C₁-C₈)alkyl, has one or more        substituents selected from CN and NO₂,    -   wherein said substituted cyclo(C₃-C₈)alkyl, has one or more        substituents selected from CN and NO₂    -   wherein each R11b is independently selected from (C₁-C₈)alkyl,        substituted (C₁-C₈)alkyl, halo(C₁-C₈)alkyl, substituted        halo(C₁-C₈)alkyl, cyclo(C₃-C₈)alkyl, substituted        cyclo(C₃-C₈)alkyl,    -   wherein each said substituted (C₁-C₈)alkyl has one or more        substituents selected from F, Cl, Br, I, CN, NO₂, OC(═O)H, OH,        S(C₁-C₈)alkyl, S(O)(C₁-C₈)alkyl, S(O)₂(C₁-C₈)alkyl, OS(O)₂aryl,        N((C₁-C₈)alkyl)₂ (wherein each (C₁-C₈)alkyl is independently        selected), aryl, substituted aryl, heterocyclyl, substituted        heterocyclyl, wherein each said substituted aryl has one or more        substituents selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,        halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,        S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈)alkyl)₂ (wherein        each (C₁-C₈)alkyl is independently selected), and oxo, wherein        each said substituted heterocyclyl has one or more substituents        selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,        halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,        S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈)alkyl)₂ (wherein        each (C₁-C₈)alkyl is independently selected), C(═O)(C₁-C₈)alkyl,        C(═O)(C₃-C₆)cycloalkyl, S(═O)₂(C₁-C₈)alkyl, NR14R15, and oxo,        wherein each said substituted-aryl has one or more substituents        selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,        halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,        S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈)alkyl)₂ (wherein        each (C₁-C₈)alkyl is independently selected), and oxo,    -   wherein said substituted halo(C₁-C₈)alkyl, has one or more        substituents selected from CN and NO₂,    -   wherein said substituted cyclo(C₃-C₈)alkyl, has one or more        substituents selected from CN and NO₂;

(l) R12 is selected from (v), H, F, Cl, Br, I, CN, (C₁-C₈)alkyl,halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy, andcyclo(C₃-C₆)alkyl;

(m) R13 is selected from (v), H, F, Cl, Br, I, CN, (C₁-C₈)alkyl,halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, and halo(C₁-C₈)alkoxy;

(n) each R14 is independently selected from H, (C₁-C₈)alkyl,(C₂-C₈)alkenyl, substituted (C₁-C₈)alkyl, halo(C₁-C₈)alkyl, substitutedhalo(C₁-C₈)alkyl), (C₁-C₈)alkoxy, cyclo(C₃-C₆)alkyl, aryl,substituted-aryl, (C₁-C₈)alkyl-aryl, (C₁-C₈)alkyl-(substituted-aryl),O—(C₁-C₈)alkyl-aryl, O—(C₁-C₈)alkyl-(substituted-aryl), heterocyclyl,substituted-heterocyclyl, (C₁-C₈)alkyl-heterocyclyl,(C₁-C₈)alkyl-(substituted-heterocyclyl), O—(C₁-C₈)alkyl-heterocyclyl,O—(C₁-C₈)alkyl-(substituted-heterocyclyl), N(R16)(R17),(C₁-C₈)alkyl-C(═O)N(R16)(R17), C(═O)(C₁-C₈)alkyl,C(═O)(halo(C₁-C₈)alkyl), C(═O)(C₃-C₆)cycloalkyl,(C₁-C₈)alkyl-C(═O)O(C₁-C₈)alkyl, C(═O)H

-   -   wherein each said substituted (C₁-C₈)alkyl has one or more        substituents selected from CN, and NO₂,    -   wherein each said substituted halo(C₁-C₈)alkyl), has one or more        substituents selected from CN, and NO₂,    -   wherein each said substituted-aryl has one or more substituents        selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,        halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,        S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈)alkyl)₂ (wherein        each (C₁-C₈)alkyl is independently selected), and oxo, and    -   wherein each said substituted-heterocyclyl has one or more        substituents selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,        halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,        (C₃-C₆)cycloalkyl S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl),        N((C₁-C₈)alkyl)₂ (wherein each (C₁-C₈)alkyl is independently        selected), heterocyclyl, C(═O)(C₁-C₈)alkyl, C(═O)O(C₁-C₈)alkyl,        and oxo, (wherein said alkyl, alkoxy, and heterocyclyl, may be        further substituted with one or more of F, Cl, Br, I, CN, and        NO₂);

(O) each R15 is independently selected from H, (C₁-C₈)alkyl,(C₂-C₈)alkenyl, substituted (C₁-C₈)alkyl, halo(C₁-C₈)alkyl, substitutedhalo(C₁-C₈)alkyl), (C₁-C₈)alkoxy, cyclo(C₃-C₆)alkyl, aryl,substituted-aryl, (C₁-C₈)alkyl-aryl, (C₁-C₈)alkyl-(substituted-aryl),O—(C₁-C₈)alkyl-aryl, O—(C₁-C₈)alkyl-(substituted-aryl), heterocyclyl,substituted-heterocyclyl, (C₁-C₈)alkyl-heterocyclyl,(C₁-C₈)alkyl-(substituted-heterocyclyl), O—(C₁-C₈)alkyl-heterocyclyl,O—(C₁-C₈)alkyl-(substituted-heterocyclyl), N(R16)(R17),(C₁-C₈)alkyl-C(═O)N(R16)(R17), C(═O)(C₁-C₈)alkyl,C(═O)(halo(C₁-C₈)alkyl), C(═O)(C₃-C₆)cycloalkyl,(C₁-C₈)alkyl-C(═O)O(C₁-C₈)alkyl, C(═O)H

-   -   wherein each said substituted (C₁-C₈)alkyl has one or more        substituents selected from CN, and NO₂,    -   wherein each said substituted halo(C₁-C₈)alkyl), has one or more        substituents selected from CN, and NO₂,    -   wherein each said substituted-aryl has one or more substituents        selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,        halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,        S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈)alkyl)₂ (wherein        each (C₁-C₈)alkyl is independently selected), and oxo, and    -   wherein each said substituted-heterocyclyl has one or more        substituents selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,        halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,        (C₃-C₆)cycloalkyl S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl),        N((C₁-C₈)alkyl)₂ (wherein each (C₁-C₈)alkyl is independently        selected), heterocyclyl, C(═O)(C₁-C₈)alkyl, C(═O)O(C₁-C₈)alkyl,        and oxo, (wherein said alkyl, alkoxy, and heterocyclyl, may be        further substituted with one or more of F, Cl, Br, I, CN, and        NO₂);

(p) each R16 is independently selected from H, (C₁-C₈)alkyl,substituted-(C₁-C₈)alkyl, halo(C₁-C₈)alkyl,substituted-halo(C₁-C₈)alkyl, cyclo(C₃-C₆)alkyl, aryl, substituted-aryl,(C₁-C₈)alkyl-aryl, (C₁-C₈)alkyl-(substituted-aryl), O—(C₁-C₈)alkyl-aryl,O—(C₁-C₈)alkyl-(substituted-aryl), heterocyclyl,substituted-heterocyclyl, (C₁-C₈)alkyl-heterocyclyl,(C₁-C₈)alkyl-(substituted-heterocyclyl), O—(C₁-C₈)alkyl-heterocyclyl,O—(C₁-C₈)alkyl-(substituted-heterocyclyl), O—(C₁-C₈)alkyl

-   -   wherein each said substituted (C₁-C₈)alkyl has one or more        substituents selected from CN, and NO₂,    -   wherein each said substituted halo(C₁-C₈)alkyl), has one or more        substituents selected from CN, and NO₂,    -   wherein each said substituted-aryl has one or more substituents        selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,        halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,        S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈)alkyl)₂ (wherein        each (C₁-C₈)alkyl is independently selected), and oxo, and    -   wherein each said substituted-heterocyclyl has one or more        substituents selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,        halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,        S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈)alkyl)₂ (wherein        each (C₁-C₈)alkyl is independently selected), and oxo;

(q) each R17 is independently selected from H, (C₁-C₈)alkyl,substituted-(C₁-C₈)alkyl, halo(C₁-C₈)alkyl,substituted-halo(C₁-C₈)alkyl, cyclo(C₃-C₆)alkyl, aryl, substituted-aryl,(C₁-C₈)alkyl-aryl, (C₁-C₈)alkyl-(substituted-aryl), O—(C₁-C₈)alkyl-aryl,O—(C₁-C₈)alkyl-(substituted-aryl), heterocyclyl,substituted-heterocyclyl, (C₁-C₈)alkyl-heterocyclyl,(C₁-C₈)alkyl-(substituted-heterocyclyl), O—(C₁-C₈)alkyl-heterocyclyl,O—(C₁-C₈)alkyl-(substituted-heterocyclyl), O—(C₁-C₈)alkyl

-   -   wherein each said substituted (C₁-C₈)alkyl has one or more        substituents selected from CN, and NO₂,    -   wherein each said substituted halo(C₁-C₈)alkyl), has one or more        substituents selected from CN, and NO₂,    -   wherein each said substituted-aryl has one or more substituents        selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,        halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,        S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈)alkyl)₂ (wherein        each (C₁-C₈)alkyl is independently selected), and oxo, and    -   wherein each said substituted-heterocyclyl has one or more        substituents selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,        halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,        S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈)alkyl)₂ (wherein        each (C₁-C₈)alkyl is independently selected), and oxo;

(r) X1 is selected from N and CR12;

(s) X2 is selected from N, CR9, and CR13;

(t) X3 is selected from N and CR9; and

(v) R12 and R13 together form a linkage containing 3 to 4 atoms selectedfrom C, N, O, and S, wherein said linkage connects back to the ring toform a 5 to 6 member saturated or unsaturated cyclic ring, wherein saidlinkage has at least one substituent X4 wherein X4 is selected from R14,N(R14)(R15), N(R14)(C(═O)R14), N(R14)(C(═S)R14),N(R14)(C(═O)N(R14)(R14)), N(R14)(C(═S)N(R14)(R14)),N(R14)(C(═O)N(R14)((C₂-C₈)alkenyl)),N(R14)(C(═S)N(R14)((C₂-C₈)alkenyl)), wherein each R14 is independentlyselected.

In another embodiment of this invention R1 may be selected from anycombination of one or more of the following —H, F, Cl, Br, I, CN, NO₂,methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl,(C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl,halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methoxy,ethoxy, (C₃)alkoxy, (C₄)alkoxy, (C₅)alkoxy, (C₆)alkoxy, (C₇)alkoxy,(C₈)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy,halo(C₅)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy.

In another embodiment of this invention R2 may be selected from anycombination of one or more of the following —H, F, Cl, Br, I, CN, NO₂,methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl,(C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl,halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methoxy,ethoxy, (C₃)alkoxy, (C₄)alkoxy, (C₅)alkoxy, (C₆)alkoxy, (C₇)alkoxy,(C₈)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy,halo(C₅)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy.

In another embodiment of this invention R3 may be selected from anycombination of one or more of the following —H, F, Cl, Br, I, CN, NO₂,methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl,(C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl,halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methoxy,ethoxy, (C₃)alkoxy, (C₄)alkoxy, (C₅)alkoxy, (C₆)alkoxy, (C₇)alkoxy,(C₈)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy,halo(C₅)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy.

In another embodiment of this invention R4 may be selected from anycombination of one or more of the following —H, F, Cl, Br, I, CN, NO₂,methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl,(C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl,halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methoxy,ethoxy, (C₃)alkoxy, (C₄)alkoxy, (C₅)alkoxy, (C₆)alkoxy, (C₇)alkoxy,(C₈)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy,halo(C₅)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy.

In another embodiment of this invention R5 may be selected from anycombination of one or more of the following —H, F, Cl, Br, I, CN, NO₂,methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl,(C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl,halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methoxy,ethoxy, (C₃)alkoxy, (C₄)alkoxy, (C₅)alkoxy, (C₆)alkoxy, (C₇)alkoxy,(C₈)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy,halo(C₅)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy.

In another embodiment of this invention R2 and R4 are selected from F,Cl, Br, I, CN, and NO₂ and R1, R3, and R5 are H.

In another embodiment of this invention R2, R3, and R4 are selected fromF, Cl, Br, I, CN, and NO₂ and R1, and R5 are H.

In another embodiment of this invention R2, R3, and R4 are independentlyselected from F and Cl and R1 and R5 are H.

In another embodiment of this invention R1 is selected from Cl and H.

In another embodiment of this invention R2 is selected from CF₃, CH₃,Cl, F, and H.

In another embodiment of this invention R3 is selected from OCH₃, CH₃,F, Cl, or H.

In another embodiment of this invention R4 is selected from CF₃, CH₃,Cl, F, and H.

In another embodiment of this invention R5 is selected from F, Cl, andH.

In another embodiment of this invention R6 may be selected from anycombination of one or more of the following—halomethyl, haloethyl,halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl,halo(C₇)alkyl, and halo(C₈)alkyl.

In another embodiment of this invention R6 is trifluoromethyl.

In another embodiment of this invention R7 may be selected from anycombination of one or more of the following —H, F, Cl, Br, and I.

In another embodiment of this invention R7 is selected from H, OCH₃, andOH.

In another embodiment of this invention R8 may be selected from anycombination of one or more of the following —H, methyl, ethyl,(C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl,halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl,halo(C₆)alkyl, halo(C₇)alkyl, and halo(C₈)alkyl.

In another embodiment of this invention R8 is selected from CH₃ and H.

In another embodiment of this invention R9 may be selected from anycombination of one or more of the following —H, F, Cl, Br, I, methyl,ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl,halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl,halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methoxy, ethoxy,(C₃)alkoxy, (C₄)alkoxy, (C₅)alkoxy, (C₆)alkoxy, (C₇)alkoxy, (C₈)alkoxy,halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(C₅)alkoxy,halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy.

In another embodiment of this invention R10 may be selected from anycombination of one or more of the following —H, F, Cl, Br, I, CN,methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl,(C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl,halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methoxy,ethoxy, (C₃)alkoxy, (C₄)alkoxy, (C₅)alkoxy, (C₆)alkoxy, (C₇)alkoxy,(C₈)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy,halo(C₅)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, halo(C₈)alkoxy,cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In another embodiment of this invention R10 may be selected from anycombination of one or more of the following —H, Cl, Br, CH₃, and CF₃.

In another embodiment of this invention R10 is selected from Br,C(═NOH)NH₂, C(═O)H, C(═O)NH₂, C(═O)OCH₂CH₃, C(═O)OH, CF₃, CH₂CH₃, CH₂OH,CH3, Cl, CN, F, H, NH₂, NHC(═O)H, NHCH₃, NO₂, OCH₃, OCHF₂, and pyridyl.

In another embodiment of this invention R11 is selected fromC(═O)N(H)N(CH₃)(C(═O)N(H)(CH₂CH₃)), C(═O)N(H)N(CH₃)(C(═O)N(H)(CH₂CF₃)),C(═O)N(H)N(CH₃)(C(═S)N(H)(CH₂CH₃)), C(═O)N(H)N(CH₃)(C(═S)N(H)(CH₂CF₃)),C(═O)N(H)CH₂CH₂N(CH₃)(C(═O)N(H)(CH₂CH₃)), and C(═O)N(H)CH₂CH₂N(CH₃)(C(═S)N(H)(CH₂CF₃)).

In another embodiment of this invention R12 may be selected from anycombination of one or more of the following —H, F, Cl, Br, I, methyl,ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl,halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl,halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, halomethoxy, haloethoxy,halo(C₃)alkoxy, halo(C₄)alkoxy, halo(C₅)alkoxy, halo(C₆)alkoxy,halo(C₇)alkoxy, and halo(C₈)alkoxy.

In another embodiment of this invention R12 is selected from CH3, and H.

In another embodiment of this invention R13 may be selected from anycombination of one or more of the following —H, F, Cl, Br, I, methyl,ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl,halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl,halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, halomethoxy, haloethoxy,halo(C₃)alkoxy, halo(C₄)alkoxy, halo(C₅)alkoxy, halo(C₆)alkoxy,halo(C₇)alkoxy, and halo(C₈)alkoxy.

In another embodiment of this invention R13 is selected from CH₃, Cl andH.

In another embodiment of this invention R12-R13 are a hydrocarbyllinkage containing CH═CHCH═CH.

In another embodiment of this invention R14 may be selected from anycombination of one or more of the following —H, methyl, ethyl,(C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl,halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl,halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methyl-aryl, ethyl-aryl,(C₃)alkyl-aryl, (C₄)alkyl-aryl, (C₅)alkyl-aryl, (C₆)alkyl-aryl,(C₇)alkyl-aryl, (C₈)alkyl-aryl, methyl-(substituted-aryl),ethyl-(substituted-aryl), (C₃)alkyl-(substituted-aryl),(C₄)alkyl-(substituted-aryl), (C₅)alkyl-(substituted-aryl),(C₆)alkyl-(substituted-aryl), (C₇)alkyl-(substituted-aryl),(C₈)alkyl-(substituted-aryl), O-methyl-aryl, O-ethyl-aryl,O—(C₃)alkyl-aryl, O—(C₄)alkyl-aryl, O—(C₅)alkyl-aryl, O—(C₆)alkyl-aryl,O—(C₇)alkyl-aryl, O—(C₈)alkyl-aryl, O-methyl-(substituted-aryl),O-ethyl-(substituted-aryl), O—(C₃)alkyl-(substituted-aryl),O—(C₄)alkyl-(substituted-aryl), O—(C₅)alkyl-(substituted-aryl),O—(C₆)alkyl-(substituted-aryl), O—(C₇)alkyl-(substituted-aryl),O—(C₈)alkyl-(substituted-aryl), methyl-heterocyclyl, ethyl-heterocyclyl,(C₃)alkyl-heterocyclyl, (C₄)alkyl-heterocyclyl, (C₅)alkyl-heterocyclyl,(C₆)alkyl-heterocyclyl, (C₇)alkyl-heterocyclyl, (C₈)alkyl-heterocyclyl,methyl-(substituted-heterocyclyl), ethyl-(substituted-heterocyclyl),(C₃)alkyl-(substituted-heterocyclyl),(C₄)alkyl-(substituted-heterocyclyl),(C₅)alkyl-(substituted-heterocyclyl),(C₆)alkyl-(substituted-heterocyclyl),(C₇)alkyl-(substituted-heterocyclyl),(C₈)alkyl-(substituted-heterocyclyl), O-methyl-heterocyclyl,O-ethyl-heterocyclyl, O—(C₃)alkyl-heterocyclyl,O—(C₄)alkyl-heterocyclyl, O—(C₅)alkyl-heterocyclyl,O—(C₆)alkyl-heterocyclyl, O—(C₇)alkyl-heterocyclyl,O—(C₈)alkyl-heterocyclyl, O-methyl-(substituted-heterocyclyl),O-ethyl-(substituted-heterocyclyl),O—(C₃)alkyl-(substituted-heterocyclyl),O—(C₄)alkyl-(substituted-heterocyclyl),O—(C₅)alkyl-(substituted-heterocyclyl),O—(C₆)alkyl-(substituted-heterocyclyl),O—(C₇)alkyl-(substituted-heterocyclyl),O—(C₈)alkyl-(substituted-heterocyclyl), methyl-C(═O)N(R16)(R17),ethyl-C(═O)N(R16)(R17), (C₃)alkyl-C(═O)N(R16)(R17),(C₄)alkyl-C(═O)N(R16)(R17), (C₅)alkyl-C(═O)N(R16)(R17),(C₆)alkyl-C(═O)N(R16)(R17), (C₇)alkyl-C(═O)N(R16)(R17), and(C₈)alkyl-C(═O)N(R16)(R17).

In another embodiment of this invention R14 may be selected from anycombination of one or more of the following —H, CH₃, CH₂CF₃,CH₂-halopyridyl, oxo-pyrrolidinyl, halophenyl, thietanyl, CH₂-phenyl,CH₂-pyridyl, thietanyl-dioxide, CH₂-halothiazolyl, C((CH₃)₂)-pyridyl,N(H)(halophenyl), CH₂-pyrimidinyl, CH₂-tetrahydrofuranyl, CH₂-furanyl,O—CH₂-halopyridyl, and CH₂C(═O)N(H)(CH₂CF₃).

In another embodiment of this invention R15 may be selected from anycombination of one or more of the following —H, methyl, ethyl,(C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl,halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl,halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methyl-aryl, ethyl-aryl,(C₃)alkyl-aryl, (C₄)alkyl-aryl, (C₅)alkyl-aryl, (C₆)alkyl-aryl,(C₇)alkyl-aryl, (C₈)alkyl-aryl, methyl-(substituted-aryl),ethyl-(substituted-aryl), (C₃)alkyl-(substituted-aryl),(C₄)alkyl-(substituted-aryl), (C₅)alkyl-(substituted-aryl),(C₆)alkyl-(substituted-aryl), (C₇)alkyl-(substituted-aryl),(C₈)alkyl-(substituted-aryl), O-methyl-aryl, O-ethyl-aryl,O—(C₃)alkyl-aryl, O—(C₄)alkyl-aryl, O—(C₅)alkyl-aryl, O—(C₆)alkyl-aryl,O—(C₇)alkyl-aryl, O—(C₈)alkyl-aryl, O-methyl-(substituted-aryl),O-ethyl-(substituted-aryl), O—(C₃)alkyl-(substituted-aryl),O—(C₄)alkyl-(substituted-aryl), O—(C₅)alkyl-(substituted-aryl),O—(C₆)alkyl-(substituted-aryl), O—(C₇)alkyl-(substituted-aryl),O—(C₈)alkyl-(substituted-aryl), methyl-heterocyclyl, ethyl-heterocyclyl,(C₃)alkyl-heterocyclyl, (C₄)alkyl-heterocyclyl, (C₅)alkyl-heterocyclyl,(C₆)alkyl-heterocyclyl, (C₇)alkyl-heterocyclyl, (C₈)alkyl-heterocyclyl,methyl-(substituted-heterocyclyl), ethyl-(substituted-heterocyclyl),(C₃)alkyl-(substituted-heterocyclyl),(C₄)alkyl-(substituted-heterocyclyl),(C₅)alkyl-(substituted-heterocyclyl),(C₆)alkyl-(substituted-heterocyclyl),(C₇)alkyl-(substituted-heterocyclyl),(C₈)alkyl-(substituted-heterocyclyl), O-methyl-heterocyclyl,O-ethyl-heterocyclyl, O—(C₃)alkyl-heterocyclyl,O—(C₄)alkyl-heterocyclyl, O—(C₅)alkyl-heterocyclyl,O—(C₆)alkyl-heterocyclyl, O—(C₇)alkyl-heterocyclyl,O—(C₈)alkyl-heterocyclyl, O-methyl-(substituted-heterocyclyl),O-ethyl-(substituted-heterocyclyl),O—(C₃)alkyl-(substituted-heterocyclyl),O—(C₄)alkyl-(substituted-heterocyclyl),O—(C₅)alkyl-(substituted-heterocyclyl),O—(C₆)alkyl-(substituted-heterocyclyl),O—(C₇)alkyl-(substituted-heterocyclyl),O—(C₈)alkyl-(substituted-heterocyclyl), methyl-C(═O)N(R16)(R17),ethyl-C(═O)N(R16)(R17), (C₃)alkyl-C(═O)N(R16)(R17),(C₄)alkyl-C(═O)N(R16)(R17), (C₅)alkyl-C(═O)N(R16)(R17),(C₆)alkyl-C(═O)N(R16)(R17), (C₇)alkyl-C(═O)N(R16)(R17), and(C₈)alkyl-C(═O)N(R16)(R17).

In another embodiment of this invention R15 may be selected from anycombination of one or more of the following —H, CH₃, CH₂CF₃,CH₂-halopyridyl, oxo-pyrrolidinyl, halophenyl, thietanyl, CH₂-phenyl,CH₂-pyridyl, thietanyl-dioxide, CH₂-halothiazolyl, C((CH₃)₂)-pyridyl,N(H)(halophenyl), CH₂-pyrimidinyl, CH₂-tetrahydrofuranyl, CH₂-furanyl,O—CH₂-halopyridyl, and CH₂C(═O)N(H)(CH₂CF₃).

In another embodiment of this invention R16 may be selected from anycombination of one or more of the following —H, methyl, ethyl,(C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl,halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl,halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methyl-aryl, ethyl-aryl,(C₃)alkyl-aryl, (C₄)alkyl-aryl, (C₅)alkyl-aryl, (C₆)alkyl-aryl,(C₇)alkyl-aryl, (C₈)alkyl-aryl, methyl-(substituted-aryl),ethyl-(substituted-aryl), (C₃)alkyl-(substituted-aryl),(C₄)alkyl-(substituted-aryl), (C₅)alkyl-(substituted-aryl),(C₆)alkyl-(substituted-aryl), (C₇)alkyl-(substituted-aryl),(C₈)alkyl-(substituted-aryl), O-methyl-aryl, O-ethyl-aryl,O—(C₃)alkyl-aryl, O—(C₄)alkyl-aryl, O—(C₅)alkyl-aryl, O—(C₆)alkyl-aryl,O—(C₇)alkyl-aryl, O—(C₈)alkyl-aryl, O-methyl-(substituted-aryl),O-ethyl-(substituted-aryl), O—(C₃)alkyl-(substituted-aryl),O—(C₄)alkyl-(substituted-aryl), O—(C₅)alkyl-(substituted-aryl),O—(C₆)alkyl-(substituted-aryl), O—(C₇)alkyl-(substituted-aryl),O—(C₈)alkyl-(substituted-aryl), methyl-heterocyclyl, ethyl-heterocyclyl,(C₃)alkyl-heterocyclyl, (C₄)alkyl-heterocyclyl, (C₅)alkyl-heterocyclyl,(C₆)alkyl-heterocyclyl, (C₇)alkyl-heterocyclyl, (C₈)alkyl-heterocyclyl,methyl-(substituted-heterocyclyl), ethyl-(substituted-heterocyclyl),(C₃)alkyl-(substituted-heterocyclyl),(C₄)alkyl-(substituted-heterocyclyl),(C₅)alkyl-(substituted-heterocyclyl),(C₆)alkyl-(substituted-heterocyclyl),(C₇)alkyl-(substituted-heterocyclyl),(C₈)alkyl-(substituted-heterocyclyl), O-methyl-heterocyclyl,O-ethyl-heterocyclyl, O—(C₃)alkyl-heterocyclyl,O—(C₄)alkyl-heterocyclyl, O—(C₅)alkyl-heterocyclyl,O—(C₆)alkyl-heterocyclyl, O—(C₇)alkyl-heterocyclyl,O—(C₈)alkyl-heterocyclyl, O-methyl-(substituted-heterocyclyl),O-ethyl-(substituted-heterocyclyl),O—(C₃)alkyl-(substituted-heterocyclyl),O—(C₄)alkyl-(substituted-heterocyclyl),O—(C₅)alkyl-(substituted-heterocyclyl),O—(C₆)alkyl-(substituted-heterocyclyl),O—(C₇)alkyl-(substituted-heterocyclyl), andO—(C₈)alkyl-(substituted-heterocyclyl).

In another embodiment of this invention R16 may be selected from anycombination of one or more of the following —H, CH₂CF₃, cyclopropyl,thietanyl, thietanyl dioxide, and halophenyl.

In another embodiment of this invention R17 may be selected from anycombination of one or more of the following —H, methyl, ethyl,(C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl,halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl,halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methyl-aryl, ethyl-aryl,(C₃)alkyl-aryl, (C₄)alkyl-aryl, (C₅)alkyl-aryl, (C₆)alkyl-aryl,(C₇)alkyl-aryl, (C₈)alkyl-aryl, methyl-(substituted-aryl),ethyl-(substituted-aryl), (C₃)alkyl-(substituted-aryl),(C₄)alkyl-(substituted-aryl), (C₅)alkyl-(substituted-aryl),(C₆)alkyl-(substituted-aryl), (C₇)alkyl-(substituted-aryl),(C₈)alkyl-(substituted-aryl), O-methyl-aryl, O-ethyl-aryl,O—(C₃)alkyl-aryl, O—(C₄)alkyl-aryl, O—(C₅)alkyl-aryl, O—(C₆)alkyl-aryl,O—(C₇)alkyl-aryl, O—(C₈)alkyl-aryl, O-methyl-(substituted-aryl),O-ethyl-(substituted-aryl), O—(C₃)alkyl-(substituted-aryl),O—(C₄)alkyl-(substituted-aryl), O—(C₅)alkyl-(substituted-aryl),O—(C₆)alkyl-(substituted-aryl), O—(C₇)alkyl-(substituted-aryl),O—(C₈)alkyl-(substituted-aryl), methyl-heterocyclyl, ethyl-heterocyclyl,(C₃)alkyl-heterocyclyl, (C₄)alkyl-heterocyclyl, (C₅)alkyl-heterocyclyl,(C₆)alkyl-heterocyclyl, (C₇)alkyl-heterocyclyl, (C₈)alkyl-heterocyclyl,methyl-(substituted-heterocyclyl), ethyl-(substituted-heterocyclyl),(C₃)alkyl-(substituted-heterocyclyl),(C₄)alkyl-(substituted-heterocyclyl),(C₅)alkyl-(substituted-heterocyclyl),(C₆)alkyl-(substituted-heterocyclyl),(C₇)alkyl-(substituted-heterocyclyl),(C₈)alkyl-(substituted-heterocyclyl), O-methyl-heterocyclyl,O-ethyl-heterocyclyl, O—(C₃)alkyl-heterocyclyl,O—(C₄)alkyl-heterocyclyl, O—(C₅)alkyl-heterocyclyl,O—(C₆)alkyl-heterocyclyl, O—(C₇)alkyl-heterocyclyl,O—(C₈)alkyl-heterocyclyl, O-methyl-(substituted-heterocyclyl),O-ethyl-(substituted-heterocyclyl),O—(C₃)alkyl-(substituted-heterocyclyl),O—(C₄)alkyl-(substituted-heterocyclyl),O—(C₅)alkyl-(substituted-heterocyclyl),O—(C₆)alkyl-(substituted-heterocyclyl),O—(C₇)alkyl-(substituted-heterocyclyl), andO—(C₈)alkyl-(substituted-heterocyclyl).

In another embodiment of this invention R17 may be selected from anycombination of one or more of the following —H, CH₂CF₃, cyclopropyl,thietanyl, thietanyl dioxide, and halophenyl.

In another embodiment of this invention X1 is CR12, X2 is CR13, and X3is CR9.

In another embodiment of this invention a heterocyclyl has preferablyabout 6 to 10 atoms in the ring structure, more preferably, 6 to 8atoms.

The molecules of Formula One will generally have a molecular mass ofabout 100 Daltons to about 1200 Daltons. However, it is generallypreferred if the molecular mass is from about 120 Daltons to about 900Daltons, and it is even more generally preferred if the molecular massis from about 140 Daltons to about 600 Daltons.

The benzyl alcohol of Formula IV, wherein R1, R2, R3, R4, R5, R6, and R7are as previously disclosed, can be synthesized in two ways. One way,disclosed in step a of Scheme I, is by treatment of the ketone ofFormula II, wherein R1, R2, R3, R4, R5, and R6 are as previouslydisclosed, with a reducing agent, such as sodium borohydride (NaBH₄),under basic conditions, such as aqueous sodium hydroxide (NaOH), in apolar protic solvent, such as methyl alcohol (MeOH) at 0° C.Alternatively, an aldehyde of Formula III, wherein R1, R2, R3, R4, R5,and R7 are as previously disclosed, is allowed to react withtrifluorotrimethylsilane in the presence of a catalytic amount oftetrabutylammonium fluoride in a polar aprotic solvent, such astetrahydrofuran (THF), as in step b of Scheme I. The compound of FormulaIV can be transformed into the compound of Formula V, wherein Y isselected from Br, Cl or I, and R1, R2, R3, R4, R5, R6, and R7 are aspreviously disclosed, by reaction with a halogenating reagent, such asN-bromosuccinimide and triethyl phosphite in a non-reactive solvent,such as dichloromethane (CH₂Cl₂) at reflux temperature to provide Y═Br,or such as thionyl chloride and pyridine in a hydrocarbon solvent, suchas toluene at reflux temperature to provide Y═Cl, as in step c of SchemeI.

Formation of the styrene coupling partners can be accomplished as inSchemes II, III IV and V.

In Scheme II, a vinylbenzoic acid of Formula VI, wherein R11 is (C═O)OHand R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed,can be converted in two steps to the vinylbenzamide of Formula VIIa,wherein R11 is (C═O)N(R14)(R15), and R8, R9, R10, R12, R13, R14, R15,and X are as previously disclosed. As in step d of Scheme II, thebenzoic acid of Formula VI is treated with oxalyl chloride in thepresence of a catalytic amount of DMF in a non-reactive solvent such asCH₂Cl₂ to form the acid chloride, which is subsequently allowed to reactwith an amine (HN(R14)(R15)), wherein R14 and R15 are as previouslydisclosed, in the presence of a base, such as triethylamine (TEA), in apolar aprotic solvent, such as THF, to provide the vinyl benzamide ofFormula VIIa, wherein R11 is (C═O)N(R14)(R15), and R8, R9, R10, R12,R13, R14, R15, X1, X2, and X3 are as previously disclosed, as in step eof Scheme II.

In Schemes III and IV, a halobenzoic acid of Formula VIII, wherein R18is Br or I, R11 is (C═O)OH and R9, R10, R12, R13, X1, X2, and X3 are aspreviously disclosed can be converted to a vinylbenzoic acid ester ofFormula VIIb1 or Formula VIIb2, wherein R18 is Br or I, R11 is(C═O)O(C₁-C₆ alkyl), and R8, R9, R10, R12, R13, X1, X2, and X3 are aspreviously disclosed. In step f of Scheme III, the halobenzoic acid ofFormula VIII, wherein R18 is Br, is treated with a base, such asn-butyllithium (n-BuLi), and DMF in a polar, aprotic solvent, such asTHF, at a temperature of about −78° C. The resulting formyl benzoic acidis allowed to react with an acid, such as sulfuric acid (H₂SO₄), in thepresence of an alcohol, such as ethyl alcohol (EtOH), as in step g, toprovide the formyl benzoic acid ethyl ester of Formula IX, wherein R11is (C═O)O(C₁-C₆ alkyl), and R9, R10, R12, R13, X1, X2, and X3 are aspreviously disclosed. The vinyl benzoic acid ester of Formula VIIb1 isaccessed via reaction of the compounds of Formula IX, with a base, suchas potassium carbonate (K₂CO₃), and methyl triphenyl phosphonium bromidein a polar aprotic solvent, such as 1,4-dioxane, at ambient temperature,as in step h of Scheme III.

In step i of Scheme IV, the halobenzoic acid of Formula VIII, whereinR18 is Br, R11 is (C═O)OH, and R8, R9, R10, R12, R13, X1, X2, and X3 areas previously disclosed, is treated with di-tert-butyl dicarbonate inthe presence of a base, such as TEA and a catalytic amount of4-(dimethylamino)pyridine (DMAP) in a polar aprotic solvent, such asTHF, at ambient temperature. The resulting benzoic acid tert-butyl esteris allowed to react with vinyl boronic anhydride pyridine complex in thepresence of a palladium catalyst, such atetrakis(triphenylphospine)palladium(0) (Pd(PPh₃)₄), and a base, such asK₂CO₃, in a non-reactive solvent such as toluene at reflux temperature,as in step j, to provide the vinyl benzoic acid ester of Formula VIIb2,wherein R11 is (C═O)O(C₁-C₆ alkyl), and R8, R9, R10, R12, R13, X1, X2,and X3 are as previously disclosed.

In step k of Scheme V, the vinyl benzoic acid ester of Formula VIIb2,wherein R10 is Br, R11 is (C═O)O(C₁-C₆ alkyl), and R8, R9, R12, R13, X1,X2, and X3 are as previously defined, can be further transformed intothe corresponding vinyl benzoic acid ester of Formula VIIb3, wherein R10is CN, R11 is (C═O)O(C₁-C₆ alkyl), and R8, R9, R12, R13, X1, X2, and X3are as previously disclosed, by reaction with copper(I) cyanide (CuCN)in a polar aprotic solvent, such as DMF, at 140° C.

Coupling of the compounds of Formula V with the compounds of FormulaVIIa, VIIb1, VIIb2 and VIIb3 can be accomplished as in Schemes VI, VII,and VIII. In step l of Scheme VI, a compound of Formula V, wherein Y,R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and thevinylbenzamide of Formula VIIa, wherein R11 is (C═O)N(R14)(R15), and R8,R9, R10, R12, R13, R14, R15, X1, X2, and X3 are as previously disclosed,are allowed to react in the presence of copper(I) chloride (CuCl) and2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at atemperature of about 180° C. to provide the molecules of Formula One,wherein R11 is (C═O)N(R14)(R15), and R1, R2, R3, R4, R5, R6, R7, R8, R9,R10, R12, R13, R14, R15, X1, X2, and X3 are as previously disclosed.

In step l of Scheme VII, the compound of Formula V, wherein Y, R1, R2,R3, R4, R5, R6, and R7 are as previously disclosed, and the vinylbenzoicacid ester of Formula VIIb1, wherein R11 is (C═O)O(C₁-C₆ alkyl), and R8,R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, areallowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent,such as 1,2-dichlorobenzene, at a temperature of about 180° C. toprovide the compounds of Formula Xa, wherein R11 is (C═O)O(C₁-C₆ alkyl),and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3are as previously disclosed. The compounds of Formula Xa are thenconverted to the molecules of Formula One, wherein R11 is(C═O)N(R14)(R15), and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13,R14, R15, X1, X2, and X3 are as previously disclosed, by either atwo-step process as disclosed in steps m and n or in one step asdisclosed in step o. In step m of Scheme VII, the ester of Formula Xa issaponified to the corresponding acid under acidic conditions, such asabout 11 Normal (N) hydrochloric acid (HCl), in a polar aprotic solvent,such as 1,4-dioxane, at about 100° C. The acid can subsequently becoupled to an amine (HN(R14)(R15)), wherein R14 and R15 are aspreviously disclosed using peptide coupling reagents, such as1-hydroxybenzotriazole (HOBt),N-(3-dimethylaminopropyl)-N′-ethyl-carbodiimide hydrochloride (EDC.HCl),benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate(PyBOP), 2-chloro-1,3-dimethylimidazolidinium hexafluorophosphate (CIP),1-hydroxy-7-azabenzotriazole (HOAt), orO-benzotriazole-N,N,N′,N′-tetramethyl-uronium-hexafluoro-phosphate(HBTU) in the presence of a base, such as N,N-diisopropylethylamine(DIPEA) or DMAP to give the molecules of Formula One, wherein R11 is(C═O)N(R14)(R15), and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13,R14, R15, X1, X2, and X3 are as previously disclosed. Alternatively, theester of Formula Xa is allowed to react with an amine (HN(R14)(R15)) inthe presence of a solution of trimethylaluminum in toluene in anon-reactive solvent, such as CH₂Cl₂, at ambient temperature, as in stepo of Scheme VII, to access the molecules of Formula One, wherein R11 is(C═O)N(R14)(R15), and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13,R14, R15, X1, X2, and X3 are as previously disclosed.

In step l of Scheme VIII, the compound of Formula V, wherein Y, R1, R2,R3, R4, R5, R6, and R7 are as previously disclosed, and the vinylbenzoicacid ester of Formula VIIb2 or VIIb3, wherein R11 is (C═O)O(C₁-C₆alkyl), and R8, R9, R10, R12, R13, X1, X2, and X3 are as previouslydisclosed, are allowed to react in the presence of CuCl and2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at atemperature of about 180° C. to provide the compounds of Formula Xb,wherein R11 is (C═O)OH, and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10,R12, R13, R14, R15, X1, X2, and X3 are as previously disclosed. Thecompounds of Formula Xb are then converted to the molecules of FormulaOne, wherein R11 is (C═O)N(R14)(R15), and R1, R2, R3, R4, R5, R6, R7,R8, R9, R10, R12, R13, R14, R15, X1, X2, and X3 are as previouslydisclosed, in one step as disclosed in step n. In step n of Scheme VIII,the acid of Formula Xb can be coupled to an amine (HN(R14)(R15)),wherein R14 and R15 are as previously disclosed, using peptide couplingreagents, such as 1-hydroxybenzotriazole (HOBt),N-(3-dimethylaminopropyl)-N′-ethyl-carbodiimide hydrochloride (EDC.HCl),benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate(PyBOP), 2-chloro-1,3-dimethylimidazolidinium hexafluorophosphate (CIP),1-hydroxy-7-azabenzotriazole (HOAt), orO-benzotriazole-N,N,N′,N′-tetramethyl-uronium-hexafluoro-phosphate(HBTU) in the presence of a base, such as DIPEA or DMAP to give themolecules of Formula One, wherein R11 is (C═O)N(R14)(R15), and R1, R2,R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, R14, R15, X1, X2, and X3 areas previously disclosed.

In step j of Scheme IX, the halobenzoketone of Formula VIIIb, whereinR18 is Br, R10 and R11 together form a linkage, having 3-4 carbon atomsand an oxo substituent and with the ring carbon atoms form a 5- or6-membered cyclic ring, and R8, R9, R12, R13, X1, X2, and X3 are aspreviously disclosed, is allowed to react with vinyl boronic anhydridepyridine complex in the presence of a palladium catalyst, such asPd(PPh₃)₄, and a base, such as K₂CO₃, in a non-reactive solvent such astoluene at reflux temperature, to provide the vinyl benzoketone ofFormula VIIb4, wherein R10 and R11 together form a linkage, having 3-4carbon atoms and an oxo substituent and with the ring carbon atoms forma 5- or 6-membered ring, and R8, R9, R12, R13, X1, X2, and X3 are aspreviously disclosed.

In step l of Scheme X, the compound of Formula V, wherein Y, R1, R2, R3,R4, R5, R6, and R7 are as previously disclosed, and the vinylbenzoketoneof Formula VIIb4 as previously disclosed, wherein R8, R9, R12, R13, X1,X2, and X3 are as previously disclosed, are allowed to react in thepresence of CuCl and 2,2-bipyridyl in a solvent, such as1,2-dichlorobenzene, at a temperature of about 180° C. to provide thecompounds of Formula Xc, wherein R10 and R11 together form a linkage,having 3-4 carbon atoms and an oxo substituent and with the ring carbonatoms form a 5- or 6-membered ring, and R1, R2, R3, R4, R5, R6, R7, R8,R9, R12, R13, X1, X2, and X3 are as previously disclosed. The compoundsof Formula Xc are then converted to the molecules of Formula Xd, whereinR10 and R11 together form a linkage, having 3-4 carbon atoms and anoxime [(C═N)(OH)] substituent and with the ring carbon atoms form a 5-or 6-membered ring, and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13,X1, X2, and X3 are as previously disclosed, in step p. In step p ofScheme X, the ketone of Formula Xc is allowed to react withhydroxylamine hydrochloride in the presence of sodium acetate and in apolar protic solvent, such as EtOH, at a temperature of about 78° C., togive the molecules of Formula Xd as previously disclosed.

The compounds of Formula Xc are also converted to the molecules ofFormula Xe, wherein R10 and R11 together form a linkage, having 3-4carbon atoms and an amine substituent and with the ring carbon atomsform a 5- or 6-membered ring, and R1, R2, R3, R4, R5, R6, R7, R8, R9,R12, R13, X1, X2, and X3 are as previously disclosed, as demonstrated instep q of Scheme XI. The ketone of Formula Xc is allowed to react withammonium acetate in the presence of sodium cyanoborohydride and in apolar protic solvent, such as MeOH, at a temperature of about 65° C., togive the molecules of Formula Xe.

The compounds of Formula Xe are converted to the molecules of FormulaOne, wherein R10 and R11 together form a linkage as previously disclosedin (u), and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X1, X2, and X3are as previously, in one step as disclosed in steps r or s. In step rof Scheme XII, the amine of Formula Xe is allowed to react with anisocyanate in a polar, aprotic solvent such as diethyl ether at ambienttemperature to provide the molecules of Formula One as previouslydisclosed. In step s of Scheme XII, the amine of Formula Xe is coupledto an acid with HOBt.H₂O and EDC.HCl in the presence of a base, such asDIPEA, in a non-reactive solvent, such as CH₂Cl₂, to give the moleculesof Formula One, as previously disclosed.

In step t of Scheme XIII, the vinyl benzyl chloride of Formula XIa,wherein R11 is —CH₂Cl and R8, R9, R10, R12, R13, X1, X2, and X3 are aspreviously defined, can be transformed into the correspondingphthalimide-protected benzyl amine of Formula XIIa, wherein R11 isCH₂N(Phthalimide), and R8, R9, R10, R12, R13, X1, X2, and X3 are aspreviously disclosed, by reaction with potassium phthalimide in a polaraprotic solvent, such as DMF, at 70° C.

In step u of Scheme XIV, the 4-methylbenzonitrile of Formula XIIIa,wherein R11 is CH₃ and R9, R10, R12, R13, X1, X2, and X3 are aspreviously defined, can be transformed into the corresponding benzylbromide of Formula XIVa, wherein R11 is CH₂Br and R8, R9, R10, R12, R13,X1, X2, and X3 are as previously disclosed, by reaction withN-bromosuccinimide (NBS) and azobisisobutyronitrile (AIBN) in anon-reactive solvent, such as carbon tetrachloride at 77° C. The nitrilegroup (CN) of Formula XIVa can be reduced to the corresponding aldehydeof Formula XVa, wherein R11 is CH₂Br and R9, R10, R12, R13, X1, X2, andX3 are as previously defined via reaction with diisobutylaluminumhydride (DIBAL-H) in an aprotic solvent, such as toluene, at 0° C.,followed by quenching with 1.0 M hydrochloric acid (HCl) as in step v ofScheme XIV. The compound of Formula XVa can be further transformed tothe corresponding phthalimide-protected benzyl amine of Formula XVIa,wherein R11 is CH₂N(Phthalimide) and R9, R10, R12, R13, X1, X2, and X3are as previously disclosed, by reaction with potassium phthalimide in apolar aprotic solvent, such as DMF, at 60° C. as in step t of SchemeXIV. In step w of Scheme XIV, the aldehyde of Formula XVIa can beconverted to the olefin of Formula XIIb, wherein R11 isCH₂N(Phthalimide) and R8, R9, R10, R12, R13, X1, X2, and X3 are aspreviously disclosed, by reaction with methyl triphenyl phosphoniumbromide in a polar aprotic solvent, such as 1,4-dioxane, in the presenceof a base, such as K₂CO₃, at ambient temperature.

The aldehyde of Formula XVa, wherein R11 is CH₂Br and R9, R10, R12, R13,X1, X2, and X3 are as previously defined, can be reacted with anucleophile, such as 2-aminopyridine, in a polar aprotic solvent, suchas N,N-dimethylacetamide (DMA), in the presence of a base, such asK₂CO₃, at ambient temperature to provide the compound of Formula XVII,wherein R11 is CH₂NH(2-pyridine) and R9, R10, R12, R13, X1, X2, and X3are as previously disclosed, as in step x of Scheme XV. In step w ofScheme XV, the compound of Formula XVII can be converted to the olefinof Formula XVIII, wherein R11 is CH₂NH(2-pyridine) and R8, R9, R10, R12,R13, X1, X2, and X3 are as previously disclosed.

In a two-step, one-pot reaction as in steps y and z of Scheme XVI, thecompound of Formula XIX can be reacted with the compounds of Formula XX,wherein R10 and R11 are Cl, X1 is N, and R9, R13, X2, and X3 are aspreviously disclosed, in the presence of a base, such as sodium hydride(NaH), and a polar aprotic solvent, such as DMF, at ambient temperatureto provide the compounds of Formula XXI, wherein R10 is Cl, R11 is(CH)NH₂CO₂CH₂CH₃, X1 is N, and R9, R13, X2, and X3 are as previouslydefined. Hydrolysis and decarboxylation of the compounds of Formula XXIcan be accomplished by reaction under acidic conditions, such as with 3N HCl, at reflux temperature, to afford the compounds of Formula XXII,wherein R10 is Cl, R11 is CH₂NH₂.HCl, X1 is N, and R9, R13, X2, and X3are as previously disclosed, as in step aa in Scheme XVI. The compoundsof Formula XXII can be further transformed to the correspondingphthalimide-protected benzyl amines of Formula XXIIIa, wherein R10 isCl, R11 is CH₂N(Phthalimide), X1 is N, and R9, R13, X1, X2, and X3 areas previously disclosed, by reaction with phthalic anhydride in thepresence of a base, such as TEA, and an aprotic solvent, such astoluene, at reflux temperature as in step ab of Scheme XVI. The bromideof Formula XXIIIa can be converted to the olefin of Formula XIIc,wherein R10 is Cl, R11 is CH₂N(Phthalimide), X1 is N, and R8, R9, R13,X2 and X3 are as previously disclosed, by reaction with vinyl boronicanhydride pyridine complex in the presence of a palladium catalyst, suchas Pd(PPh₃)₄, and a base, such as K₂CO₃, in a non-reactive solvent suchas toluene at reflux temperature, as in step ac of Scheme XVI.

In step u of Scheme XVII, the 4-methylnaphthonitrile of Formula XIIIb,wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbonatoms and with the ring carbon atoms form a 6-membered aromatic ring,R11 is CH₃, and R12, R13, X1 and X2 are as previously defined, can betransformed into the corresponding naphthyl bromide of Formula XIVb,wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbonatoms and with the ring carbon atoms form a 6-membered aromatic ring,R11 is CH₂Br, and R12, R13, X1 and X2 are as previously disclosed, byreaction with N-bromosuccinimide (NBS) and azobisisobutyronitrile (AIBN)in a non-reactive solvent, such as carbon tetrachloride at 77° C. Thenitrile group (CN) of Formula XIVb can be reduced to the correspondingaldehyde of Formula XVb, wherein X3 is CR9, R10 and X3 together form alinkage having 4 carbon atoms and with the ring carbon atoms form a6-membered aromatic ring (or if desired a non-aromatic ring), R11 isCH₂Br, and R12, R13, X1 and X2 are as previously defined via reactionwith diisobutylaluminum hydride (DIBAL-H) in an aprotic solvent, such astoluene, at 0° C., followed by quenching with 1.0 M HCl as in step v ofScheme XVII. The compound of Formula XVb can be further transformed tothe corresponding phthalimide-protected benzyl amine of Formula XVIb,wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbonatoms and with the ring carbon atoms form a 6-membered aromatic ring,R11 is CH₂N(Phthalimide), and R12, R13, X1 and X2 are as previouslydisclosed, by reaction with potassium phthalimide in a polar aproticsolvent, such as DMF, at 60° C. as in step t of Scheme XVII. In step wof Scheme XVII, the aldehyde of Formula XVIb can be converted to theolefin of Formula XIId, wherein X3 is CR9, R10 and X3 together form alinkage having 4 carbon atoms and with the ring carbon atoms form a6-membered aromatic ring, R11 is CH₂N(Phthalimide), and R8, R12, R13, X1and X2 are as previously disclosed, by reaction with methyl triphenylphosphonium bromide in a polar aprotic solvent, such as 1,4-dioxane, inthe presence of a base, such as K₂CO₃, at ambient temperature.

The compound of Formula XXIV, wherein R11 is NHNH₂.HCl and R9, R10, R12,R13, X1, X2, and X3 are as previously disclosed, can be transformed intothe corresponding phthalimide-protected hydrazine of Formula XXV,wherein R11 is NHN(Phthalimide) and R9, R10, R12, R13, X1, X2, and X3are as previously disclosed, by reaction with phthalic anhydride inglacial acetic acid at reflux temperature as in step ad of Scheme XVIII.The bromide of Formula XXV can be converted to the olefin of FormulaXIIe, wherein R11 is NHN(Phthalimide) and R8, R9, R10, R13, X1, X2 andX3 are as previously disclosed, by reaction with vinyl boronic anhydridepyridine complex in the presence of a palladium catalyst, such asPd(PPh₃)₄, and a base, such as K₂CO₃, in a polar aprotic solvent such as1,2-dimethoxyethane at 150° C. under microwave conditions, as in step aeof Scheme XVIII.

In step af of Scheme XIX, the compound of Formula XXVI, wherein R11 isB(OH)₂, and R8, R9, R10, R12, R13, X1, X2, and X3 are as previouslydisclosed, are allowed to react with 2-hydroxyisoindoline-1,3-dione inthe presence of CuCl and pyridine in a solvent, such as1,2-dichlorobenzene, at ambient temperature to provide the compound ofFormula XIIf, wherein R11 is ON(Phthalimide) and R8, R9, R10, R12, R13,X1, X2, and X3 are as previously disclosed.

In step l of Scheme XX, the compound of Formula V, wherein Y, R1, R2,R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds ofFormula XIIa, wherein R11 is CH₂N(Phthalimide) and R8, R9, R10, R12,R13, X1, X2, and X3 are as previously disclosed, are allowed to react inthe presence of CuCl and 2,2-bipyridyl in a solvent, such as1,2-dichlorobenzene, at a temperature of about 180° C. to provide thecorresponding compounds of Formula XXVIIa, wherein R11 isCH₂N(Phthalimide) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13,X1, X2, and X3 are as previously disclosed. The phthalimide protectinggroup in the compounds of Formula XXVIIa is removed as in step ag ofScheme XX by reaction with hydrazine hydrate in a polar protic solventsuch as EtOH at 90° C. to provide the compounds of Formula XXVIIIa,wherein R11 is CH₂NH₂ and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12,R13, X1, X2, and X3 are as previously disclosed. The compounds ofFormula XXVIIIa can be transformed into the compounds of Formula One,wherein R11 is CH₂N(C═O)(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9,R10, R12, R13, X1, X2, and X3 are as previously disclosed, by acylationwith an anhydride, such as acetic anhydride, and a base, such as TEA, ina non-reactive solvent such as CH₂Cl₂ at 0° C. as in step ah₁ of SchemeXX.

In step l of Scheme XXI, the compound of Formula V, wherein Y, R1, R2,R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds ofFormula XIIb, wherein R11 is CH₂N(Phthalimide) and R8, R9, R10, R12,R13, X1, X2, and X3 are as previously disclosed, are allowed to react inthe presence of CuCl and 2,2-bipyridyl in a solvent, such as1,2-dichlorobenzene, at a temperature of about 180° C. to provide thecorresponding compounds of Formula XXVIIb, wherein R11 isCH₂N(Phthalimide) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13,X1, X2, and X3 are as previously disclosed. The phthalimide protectinggroup in the compounds of Formula XXVIIb is removed as in step ag ofScheme XXI by reaction with hydrazine hydrate in a polar protic solventsuch as EtOH at 90° C. to provide the compounds of Formula XXVIIIb,wherein R11 is CH₂NH₂ and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12,R13, X1, X2, and X3 are as previously disclosed. The compounds ofFormula XXVIIIb can be transformed into the compounds of Formula One,wherein R11 is CH₂N(C═O)(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9,R10, R12, R13, X1, X2, and X3 are as previously disclosed, by reactionwith an acid in the presence of HOBt.H₂O, EDC.HCl and a base, such asDIPEA, in a polar aprotic solvent, such as DMF, as in step ah_(2a) ofScheme XXI.

In another embodiment, the compounds of Formula XXVIIIb can betransformed into the compounds of Formula One, wherein R11 isCH₂N(C═S)(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13,X1, X2, and X3 are as previously disclosed, by reaction with a thioacidin the presence of HOBt.H₂O, EDC.HCl and a base, such as DIPEA, in apolar aprotic solvent, such as DMF, as in step ah₂ of Scheme XXI.

In another embodiment, the compounds of Formula XXVIIIb can betransformed into the compounds of Formula One, wherein R11 isCH₂N(C═O)N(R14)(R15) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12,R13, X1, X2, and X3 are as previously disclosed, in two steps. The firststep (step ah_(3a) of Scheme XXI) involves reaction with an aldehyde ina polar protic solvent such as MeOH, followed by reaction with sodiumborohydride. The second step (step ah_(3b) of Scheme XXI) involvesacylation with an acid chloride, such as cyclopropylcarbonyl chloride,and a base, such as TEA, in a non-reactive solvent such as CH₂Cl₂ atambient temperature of Scheme XXI.

In another embodiment, the compounds of Formula XXVIIIb can betransformed into the compounds of Formula One, wherein R11 isCH₂N(C═O)N(R14)(R15) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12,R13, X1, X2, and X3 are as previously disclosed, by reaction with anisocyanate (step ai₁ of Scheme XXI) or a carbamoyl chloride (step ai₁ ofScheme XXI) in the presence of a base such as TEA and in a non-reactivesolvent such as CH₂Cl₂ at 0° C.

In another embodiment, the compounds of Formula XXVIIIb can betransformed into the compounds of Formula One, wherein R11 isCH₂N(C═S)N(R14)(R15) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12,R13, X1, X2, and X3 are as previously disclosed, by reaction with anisothiocyanate in the presence of a base such as TEA and in anon-reactive solvent such as CH₂Cl₂ at 0° C., as in steps aj of SchemeXXI.

In another embodiment, the compounds of Formula XXVIIIb can betransformed into the compounds of Formula One, wherein R11 isCH₂N(C═O)O(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13,X1, X2, and X3 are as previously disclosed, by reaction with adicarbonate, such as di-tert-butyl dicarbonate in the presence of a basesuch as TEA and in a non-reactive solvent such as CH₂Cl₂ at ambienttemperature, as in steps ak of Scheme XXI.

In yet another embodiment, the compounds of Formula XXVIIIb can betransformed into the compounds of Formula One, wherein R11 isCH₂N(C═O)(C═O)O(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12,R13, X1, X2, and X3 are as previously disclosed, by reaction with achlorooxalic acid ester, such as 2-chloro-2-oxoacetate in the presenceof a base such as TEA and in a non-reactive solvent such as CH₂Cl₂ at 0°C., as in steps al of Scheme XXI.

In step l of Scheme XXII, the compound of Formula V, wherein Y, R1, R2,R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds ofFormula XIIc, wherein R10 is Cl, R11 is CH₂N(Phthalimide), X1 is N, andR8, R9, R12, R13, X2, and X3 are as previously disclosed, are allowed toreact in the presence of CuCl and 2,2-bipyridyl in a solvent, such as1,2-dichlorobenzene, at a temperature of about 180° C. to provide thecorresponding compounds of Formula XXVIIc, wherein R10 is Cl, R11 isCH₂N(Phthalimide), X1 is N, and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12,R13, X2, and X3 are as previously disclosed. The phthalimide protectinggroup in the compounds of Formula XXVIIc is removed as in step ag ofScheme XXII by reaction with hydrazine hydrate in a polar protic solventsuch as EtOH at 90° C. to provide the compounds of Formula XXVIIIc,wherein R10 is Cl, R11 is CH₂NH₂, X1 is N, and R1, R2, R3, R4, R5, R6,R7, R8, R9, R12, R13, X2, and X3 are as previously disclosed. Thecompounds of Formula XXVIIIc can be transformed into the compounds ofFormula One, wherein R10 is Cl, R11 is CH₂N(C═O)(R14), X1 is N, and R1,R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X2, and X3 are as previouslydisclosed, by reaction with an acid in the presence of HOBt.H₂O, EDC.HCland a base, such as DIPEA, in a polar aprotic solvent, such as CH₂Cl₂,as in step ah_(2b) of Scheme XXII.

In step l of Scheme XXIII, the compound of Formula V, wherein Y, R1, R2,R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds ofFormula XIId, wherein X3 is CR9, R10 and X3 together form a linkagehaving 4 carbon atoms and with the ring carbon atoms form a 6-memberedaromatic ring (or if desired a non-aromatic ring), R11 isCH₂N(Phthalimide) and R8, R9, R12, R13, X1 and X2 are as previouslydisclosed, are allowed to react in the presence of CuCl and2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at atemperature of about 180° C. to provide the corresponding compounds ofFormula XXVIId, wherein X3 is CR9, R10 and X3 together form a linkagehaving 4 carbon atoms and with the ring carbon atoms form a 6-memberedaromatic ring, R11 is CH₂N(Phthalimide) and R1, R2, R3, R4, R5, R6, R7,R8, R9, R12, R13, X1 and X2 are as previously disclosed. The phthalimideprotecting group in the compounds of Formula XXVIId is removed as instep ag of Scheme XXIII by reaction with hydrazine hydrate in a polarprotic solvent such as EtOH at 90° C. to provide the compounds ofFormula XXVIIId, wherein X3 is CR9, R10 and X3 together form a linkagehaving 4 carbon atoms and with the ring carbon atoms form a 6-memberedaromatic ring, R11 is CH₂NH₂ and R1, R2, R3, R4, R5, R6, R7, R8, R9,R12, R13, X1 and X2 are as previously disclosed. The compounds ofFormula XXVIIId can be transformed into the compounds of Formula One,wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbonatoms and with the ring carbon atoms form a 6-membered aromatic ring,R11 is CH₂N(C═O)(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13,X1 and X2 are as previously disclosed, by reaction with an acid in thepresence of HOBt.H₂O, EDC.HCl and a base, such as DIPEA, in a polaraprotic solvent, such as CH₂Cl₂, as in step ah_(2b) of Scheme XXIII

In another embodiment, the compounds of Formula XXVIIId can betransformed into the compounds of Formula One, wherein X3 is CR9, R10and X3 together form a linkage having 4 carbon atoms and with the ringcarbon atoms form a 6-membered aromatic ring, R11 isCH₂N(C═O)N(R14)(R15) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12,R13, X1 and X2 are as previously disclosed, by reaction with anisocyanate in the presence of a base such as TEA and in a non-reactivesolvent such as CH₂Cl₂ at 0° C. as in step ai₁ of Scheme XXIII.

In step l of Scheme XXIV, the compound of Formula V, wherein Y, R1, R2,R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds ofFormula XIIe, wherein R11 is NHN(Phthalimide) and R8, R9, R12, R13, X1,X2, and X3 are as previously disclosed, are allowed to react in thepresence of CuCl and 2,2-bipyridyl in a solvent, such as1,2-dichlorobenzene, at a temperature of about 180° C. to provide thecorresponding compounds of Formula XXVIIe, wherein R11 isNHN(Phthalimide) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X1,X2, and X3 are as previously disclosed. The phthalimide protecting groupin the compounds of Formula XXVIIe is removed as in step ag of SchemeXXIV by reaction with hydrazine hydrate in a polar protic solvent suchas EtOH at 90° C. to provide the compounds of Formula XXVIIIe, whereinR11 is NHNH₂ and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X1, X2,and X3 are as previously disclosed. The compounds of Formula XXVIIIe canbe transformed into the compounds of Formula One, wherein R11 isNHN(C═O)(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X1, X2,and X3 are as previously disclosed, by reaction with an acid in thepresence of HOBt.H₂O, EDC.HCl and a base, such as DIPEA, in a polaraprotic solvent, such as CH₂Cl₂, as in step ah_(2b) of Scheme XXIV.

In step l of Scheme XXV, the compound of Formula V, wherein Y, R1, R2,R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds ofFormula XIIf, wherein R11 is ON(Phthalimide) and R8, R9, R10, R12, R13,X1, X2, and X3 are as previously disclosed, are allowed to react in thepresence of CuCl and 2,2-bipyridyl in a solvent, such as1,2-dichlorobenzene, at a temperature of about 180° C. to provide thecorresponding compounds of Formula XXVIIf, wherein R11 isON(Phthalimide) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13,X1, X2, and X3 are as previously disclosed. The phthalimide protectinggroup in the compounds of Formula XXVIIf is removed as in step ag ofScheme XXV by reaction with hydrazine hydrate in a polar protic solventsuch as EtOH at 90° C. to provide the compounds of Formula XXVIIIf,wherein R11 is ONH₂ and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12,R13, X1, X2, and X3 are as previously disclosed. The compounds ofFormula XXVIIIf can be transformed into the compounds of Formula One,wherein R11 is ON(C═O)(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10,R12, R13, X1, X2, and X3 are as previously disclosed, by reaction withan acid in the presence of HOBt.H₂O, EDC.HCl and a base, such as DIPEA,in a polar aprotic solvent, such as CH₂Cl₂, as in step ah_(2b) of SchemeXXV.

In step l of Scheme XXVI, the compound of Formula V, wherein Y, R1, R2,R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds ofFormula XVIII, wherein R11 is CH₂NH(2-pyridine) and R8, R9, R10, R12,R13, X1, X2, and X3 are as previously disclosed, are allowed to react inthe presence of CuCl and 2,2-bipyridyl in a solvent, such as1,2-dichlorobenzene, at a temperature of about 180° C. to provide thecorresponding compounds of Formula One, wherein R11 isCH₂NH(2-pyridine), and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12,R13, X1, X2, and X3 are as previously disclosed.

The compounds of Formula One can be further elaborated by standardmethods. For example, when R11 contains a thioether, the thioether canbe oxidized to the sulfone by treatment with oxone in the presence of anacetone:water mixture at ambient temperature. When R11 contains anoxalate ester, the compound of Formula One can be transformed into thecorresponding oxalamide by reaction with an amine hydrochloride and asolution of trimethylaluminum in toluene in a non-reactive solvent suchas CH₂Cl₂.

In Scheme XXVII, a fluorobenzaldehyde of Formula XXIX, wherein R10, X1,X2, and X3 are as previously disclosed can be converted to a(1,2,4-triazol-1-yl)benzaldehyde of Formula XXX, wherein R11 is asubstituted or unsubstituted 1,2,4-triazol-1-yl group, and R10, X1, X2,and X3 are as previously disclosed by reaction with a substituted orunsubstituted 1,2,4-triazole in the presence of a base, such aspotassium carbonate, in a solvent such as DMF as in step aj. In step ak,the (1,2,4-triazol-1-yl)benzaldehyde of Formula XXX is converted to a(1,2,4-triazol-1-yl)vinyl benzene of Formula XXXIa wherein R11 is asubstituted or unsubstituted 1,2,4-triazol-1-yl group, and R8, R10, X1,X2, and X3 are as previously disclosed by reaction with triphenylphosphonium bromide in the presence of a base, such as potassiumcarbonate, in an aprotic solvent, such as 1,4-dioxane.

In Scheme XXVIII, a bromofluorobenzene of Formula XXXII, wherein R10,X1, X2, and X3 are as previously disclosed can be converted to a(1,2,4-triazol-1-yl)vinylbenzene of Formula XXXIb, wherein R11 is asubstituted or unsubstituted 1,2,4-triazol-1-yl group, and R8, R10, X1,X2, and X3 are as previously disclosed in two steps. In step al, thebromofluorobenzene is reacted with a substituted or unsubstituted1,2,4-triazole in the presence of a base, such as potassium carbonate,in a solvent such as DMF to generate the(1,2,4-triazol-1-yl)bromobenzene. In step c/, the(1,2,4-triazol-1-yl)bromobenzene is reacted with vinyl boronic anhydridepyridine complex in the presence of a catalyst, such as Pd (PPh₃)₄, anda base, such as potassium carbonate in a solvent such as toluene.

Coupling of the compounds of Formula V with compounds of Formula XXXIaand XXXIb can be accomplished as in Schemes XXIX. In step 1, a compoundof Formula V, wherein Y is Br, R1, R2, R3, R4, R5, R6, and R7 are aspreviously disclosed, and a vinylbenzene of Formula XXXIa or XXXIb,wherein R11 is a substituted or unsubstituted 1,2,4-triazol-1-yl group,and R8, R9, R10, X1, X2, and X3 are as previously disclosed, are allowedto react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as1,2-dichlorobenzene, at a temperature of about 180° C. to provide themolecules of Formula One, wherein R11 is a substituted or unsubstituted1,2,4-triazol-1-yl group, and R1, R2, R3, R4, R5, R6, R7, R8, R10, X1,X2, and X3 are as previously disclosed.

In Scheme XXX, compounds of Formula XXXIII wherein R11 is a3-nitro-1,2,4-triazol-1-yl group, and R1, R2, R3, R4, R5, R6, R7, R8,R10, X1, X2, and X3 are as previously disclosed can be converted tocompounds of Formula One, wherein R11 is a 3-amido-1,2,4-triazol-1-ylgroup, and R1, R2, R3, R4, R5, R6, R7, R8, R10, X1, X2, and X3 are aspreviously disclosed by a two-step process. In step am, the3-nitro-1,2,4-triazol-1-yl group is reduced to a3-amino-1,2,4-triazol-1-yl group in the presence of zinc dust andammonium chloride in a protic solvent, such as MeOH. In step an, the3-amino-1,2,4-triazol-1-yl group is acylated with an acid chloride, suchas cyclopropylcarbonyl chloride or acetyl chloride, in the presence of abase, such as TEA, in a solvent such as CH₂Cl₂.

In step ao of Scheme XXXI, a bromophenyl methyl ketone of Formula XXXIVwherein R10, X1, X2, and X3 are as previously disclosed is converted toan phenyl methyl ketone of the Formula XXXV wherein R11 is a1,2,4-triazol-1-yl group, and R10, X1, X2, and X3 are as previouslydisclosed by treatment with 1,2,4-triazole in the presence of a base,such as cesium carbonate, and a catalyst, such as copper iodide, in asolvent, such as DMF. In step ap, the 1,2,4-triazolylacetophenone ofFormula XXXV is converted to the trimethylsilyl enol ether of FormulaXXXVI by treatment with trimethylsilyl triflluoromethanesulfonate in thepresence of a base, such as TEA, in an aprotic solvent, such as CH₂Cl₂.In step aq, the silyl enol ether is reacted with a compound of FormulaV, wherein Y is Br, R1, R2, R3, R4, R5, R6, and R7 are as previouslydisclosed in the presence of CuCl and 2,2-bipyridyl in a solvent, suchas 1,2-dichlorobenzene at a temperature of about 180° C. to generate aketone of the Formula XXXVII, wherein R11 is a 1,2,4-triazol-1-yl group,and R1, R2, R3, R4, R5, R6, R7, R10, X1, X2, and X3 are as previouslydisclosed. In step ar, the ketone of the Formula XXXVII is treated withmethylmagnesium bromide in an aprotic solvent, such as THF to generatethe tertiary alcohol. The tertiary alcohol then undergoes an eliminationreaction when treated with a catalytic amount of p-toluenesulfonic acidin a solvent, such as toluene, when heated to a temperature to allowazeotropic removal of water to produce compounds of Formula One whereinR11 is a 1,2,4-triazol-1-yl group, R8 is methyl, and R1, R2, R3, R4, R5,R6, R7, R10, X1, X2, and X3 are as previously disclosed, as in step as.

In Scheme XXXII, a compound of Formula XXXVIII, wherein R10 and R11together form a linkage, having 3-4 carbon atoms and an oxo substituentand with the ring carbon atoms form a 5- or 6-membered cyclic ring, andR1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previouslydisclosed is converted to a molecule of Formula One, wherein R10 and R11together form a linkage, having 3-4 carbon atoms and an alkylaminesubstituent with the ring carbon atoms form a 5- or 6-membered cyclicring and R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are aspreviously disclosed, by treatment with an alkylamine, such as3,3,3-trifluoropropylamine, in the presence of a reducing agent, such assodium cyanoborohydride, in a solvent, such as DCE.

In Scheme XXXIII, a compound of Formula XXXIX, wherein X1, X2, and X3are as previously disclosed is converted to a molecule of Formula XL,wherein X1, X2, and X3 are as previously disclosed, by treatment with areducing agent, such as sodium cyanoborohydride, in a solvent, such asacetic acid, as in step au. In step av, the nitrogen atom is protectedwith a tert-butyloxycarbonyl (BOC) group by reaction with di-tert-butyldicarbonate in the presence of a catalyst, such as DMAP, in a solvent,such as acetonitrile. The bromide of Formula XL can be converted to theolefin of Formula XLI, wherein R8, X1, X2 and X3 are as previouslydisclosed, by reaction with potassium vinyl trifluoroborate in thepresence of a palladium catalyst, such as PdCl₂(dppf), and a base, suchas K₂CO₃, in a polar aprotic solvent such as DMSO at 100° C., as in stepaw.

In Scheme XXXIV, a compound of Formula XXXIX, wherein X1, X2, and X3 areas previously disclosed is converted to a molecule of Formula XLII,wherein X1, X2, and X3 are as previously disclosed in two steps. In stepax, the olefin is formed by treatment of the bromide with potassiumvinyl trifluoroborate in the presence of a palladium catalyst, such asPdCl₂, and a ligand, such as triphenylphosphine, and a base, such asCs₂CO₃, in a solvent mixture such as THF/H₂O. In step ay, the nitrogenatom is protected with a tert-butyloxycarbonyl (BOC) group by reactionwith di-tert-butyl dicarbonate in the presence of a catalyst, such asDMAP, in a solvent, such as acetonitrile.

In step l of Scheme XXXV, the compound of Formula V, wherein Y, R1, R2,R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds ofFormula XLI or XLII, wherein R8, X1, X2 and X3 are as previouslydisclosed, are allowed to react in the presence of CuCl and2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at atemperature of about 150° C. to provide the corresponding compounds ofFormula XLIIIa or XLIIIb, wherein R1, R2, R3, R4, R5, R6, R7, R8, X1,X2, and X3 are as previously disclosed.

In Scheme XXXVI, a compound of Formula XLIIIa, wherein R1, R2, R3, R4,R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed is convertedto a molecule of Formula XLIV, wherein R1, R2, R3, R4, R5, R6, R7, R8,X1, X2, and X3 are as previously disclosed by treatment withtrifluoroacetic acid, in a solvent such as CH₂Cl₂, as in step az.Compounds of the Formula XLIV can then be transformed into compounds ofthe Formula XLV wherein R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3are as previously disclosed, in two steps. In step ba, the indoline istreated with sodium nitrite (NaNO₂), in an acid, such as concentratedHCl, at a temperature around 5° C., to form the nitrosoindole. In stepbb, the nitrosoindole is reacted with ammonium chloride in the presenceof zinc powder in a protic solvent, such as MeOH. In step bc, compoundsof the Formula XLV are transformed into compounds of the Formula XLVI,wherein X4 is N(R14)(C(═O)R14) and R1, R2, R3, R4, R5, R6, R7, R8, X1,X2, and X3 are as previously disclosed, by treatment with and acid, suchas 3,3,3-trifluoropropanoic acid, PyBOP, and a base, such as DIPEA, in apolar aprotic solvent, such as CH₂Cl₂.

In Scheme XXXVII, a compound of Formula XLIIIb, wherein R1, R2, R3, R4,R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed is convertedto an indole of Formula XLVII, wherein R1, R2, R3, R4, R5, R6, R7, R8,X1, X2, and X3 are as previously disclosed by treatment withtrifluoroacetic acid, in a solvent such as CH₂Cl₂, as in step bd.Compounds of the Formula XLVII can be transformed into compounds of theFormula XLVIII wherein R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3are as previously disclosed, by reaction with4-nitrophenyl-2-((tert-butoxycarbonyl)amino)acetate in the presence ofpotassium fluoride and a crown ether, such as 18-crown-6-ether, in asolvent, such as acetonitrile, as in step be. Compounds of the FormulaXLVIII can be transformed into compounds of the Formula XLIX, whereinR1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previouslydisclosed in two steps. In step bf, the Boc group is removed bytreatment with trifluoroacetic acid, in a solvent such as CH₂Cl₂. Instep bg, the amine is treated with 3,3,3-trifluoropropanoic acid, PyBOP,and a base, such as DIPEA, in a polar aprotic solvent, such as CH₂Cl₂.

In Scheme XXXVIII, a compound of Formula L, wherein X1, X2, and X3 areas previously disclosed is converted to a compound of the Formula LI,wherein X1, X2, and X3 are as previously disclosed by treatment withcopper (II) sulfate pentahydrate and Zn powder in a base, such as sodiumhydroxide as in step bh. Compounds of the Formula LI can be transformedinto compounds of the Formula LII wherein X1, X2, and X3 are aspreviously disclosed, by reaction with hydrazine, in a solvent such aswater, at a temperature around 95° C., as in step bi. In step bj, theolefin of the Formula LIII wherein X1, X2, and X3 are as previouslydisclosed is formed by treatment of the bromide with potassium vinyltrifluoroborate in the presence of a palladium catalyst, such asPdCl₂(dppf), and a base, such as K₂CO₃, in a solvent mixture such asDMSO. Compounds of the Formula LIV, wherein X1, X2, and X3 are aspreviously disclosed, can be formed from compounds of the Formula LIIIby reaction with ethyl bromoacetate, in the presence of a base, such asCs₂CO₃, in a solvent, such as DMF.

In step l of Scheme XXXIX, the compound of Formula V, wherein Y, R1, R2,R3, R4, R5, R6, and R7 are as previously disclosed, and the compound ofFormula LIV, wherein R8, X1, X2 and X3 are as previously disclosed, areallowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent,such as 1,2-dichlorobenzene, at a temperature of about 180° C. toprovide the corresponding compound of Formula LV, wherein R1, R2, R3,R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed. Thecompound of Formula LV can be further transformed into a compound of theFormula LVI, wherein R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 areas previously disclosed, in two steps. In step bl, the ester ishydrolyzed to the acid in the presence of HCl and acetic acid, at atemperature of about 100° C. In step bm, the acid is treated with anamine, such as 2,2,2-trifluoroethylamine, PyBOP, and a base, such asDIPEA, in a polar aprotic solvent, such as CH₂Cl₂.

In step bn of Scheme XL, carboxylic acids of the Formula LVII, whereinR11 is C(═O)OH and R8, R10, X1, X2, and X3 are as previously disclosedand compounds of the Formula V, wherein Y is Br and R1, R2, R3, R4, R5,R6, and R7 are as previously disclosed are allowed to react in thepresence of CuCl and 2,2-bipyridyl in a solvent, such as N-methylpyrrolidine, at a temperature of about 150° C. to afford compounds ofFormula LVIII, wherein R11 is (C═O)OH and R1, R2, R3, R4, R5, R6, R7,R8, R9, R10, X1, X2, and X3 are as previously disclosed. Compounds ofthe Formula LVIII can be further transformed to the correspondingbenzamides of Formula LIX, wherein R11 is (C═O)N(R14)(R15), and R1, R2,R3, R4, R5, R6, R7, R8, R9, R10, X1, X2, and X3 are as previouslydisclosed, by treatment with an amine, such as2-amino-N-(2,2,2-trifluoroethyl)acetamide, PyBOP, and a base, such asDIPEA, in a polar aprotic solvent, such as CH₂Cl₂, as in step bo.

EXAMPLES

The examples are for illustration purposes and are not to be construedas limiting the invention disclosed in this document to only theembodiments disclosed in these examples.

Starting materials, reagents, and solvents that were obtained fromcommercial sources were used without further purification. Anhydroussolvents were purchased as Sure/Seal™ from Aldrich and were used asreceived. Melting points were obtained on a Thomas Hoover Unimeltcapillary melting point apparatus or an OptiMelt Automated Melting PointSystem from Stanford Research Systems and are uncorrected. Molecules aregiven their known names, named according to naming programs within ISISDraw, ChemDraw, or ACD Name Pro. If such programs are unable to name amolecule, the molecule is named using conventional naming rules. ¹H NMRspectral data are in ppm (δ) and were recorded at 300, 400, or 600 MHz,and ¹³C NMR spectral data are in ppm (δ) and were recorded at 75, 100,or 150 MHz, unless otherwise stated.

Example 1 Preparation of1-(1-Bromo-2,2,2-trifluoroethyl)-3,5-dichlorobenzene (AI1)

Step 1 Method A. 1-(3,5-Dichlorophenyl)-2,2,2-trifluoroethanol (AI2)

To a stirred solution of 1-(3,5-dichlorophenyl)-2,2,2-trifluoroethanone(procured from Rieke Metals, UK; 5.0 grams (g), 20.5 millimoles (mmol))in MeOH (100 mL) at 0° C. were added sodium borohydride (NaBH₄; 3.33 g,92.5 mL) and 1 Normal (N) aqueous sodium hydroxide solution (NaOH; 10mL). The reaction mixture was warmed to 25° C. and stirred for 2 hours(h). After the reaction was deemed complete by thin layer chromatography(TLC), saturated (satd) aqueous (aq) ammonium chloride (NH₄Cl) solutionwas added to the reaction mixture, and the mixture was concentratedunder reduced pressure. The residue was diluted with diethyl ether(Et₂O) and washed with water (H₂O; 3×50 mL). The organic layer was driedover sodium sulfate (Na₂SO₄) and concentrated under reduced pressure toafford the title compound as a liquid (4.0 g, 79%): ¹H NMR (400 MHz,CDCl₃) δ 7.41 (m, 3H), 5.00 (m, 2H), 2.74 (s, 1H); ESIMS m/z 242.97([M−H]⁻).

Step 1 Method B. 1-(3,5-Dichlorophenyl)-2,2,2-trifluoroethanol (AI2)

To a stirred solution of 3,5-dichlorobenzaldehyde (10 g, 57 mmol) in THF(250 mL) were added trifluoromethyltrimethylsilane (9.79 g, 69.2 mmol)and a catalytic amount of tetrabutylammonium fluoride (TBAF). Thereaction mixture was stirred at 25° C. for 8 h. After the reaction wasdeemed complete by TLC, the reaction mixture was diluted with 3 Nhydrochloric acid (HCl) and then was stirred for 16 h. The reactionmixture was diluted with H₂O and was extracted with ethyl acetate(EtOAc; 3×). The combined organic extracts were washed with brine, driedover Na₂SO₄, and concentrated under reduced pressure to afford the titlecompound as a liquid (8.41 g, 60%).

The following compounds were made in accordance with the proceduresdisclosed in Step 1 Method B of Example 1 above.

2,2,2-Trifluoro-1-(3,4,5-trichlorophenyl)ethanol (AI3)

The product was isolated as a pale yellow liquid (500 mg, 65%): ¹H NMR(400 MHz, CDCl₃) δ 7.45 (s, 2H), 5.00 (m, 1H), 2.80 (s, 1H); ESIMS m/z278 ([M+H]⁺); IR (thin film) 3420, 1133, 718 cm⁻¹.

1-(3,5-Dichloro-4-fluorophenyl)-2,2,2-trifluoroethanol (AI4)

The product was isolated as a pale yellow liquid (500 mg, 65%): ¹H NMR(400 MHz, CDCl₃) δ 7.41 (s, 2H), 5.00 (m, 1H), 2.80 (s, 1H); ESIMS m/z262 ([M+H]⁺); IR (thin film) 3420, 1133, 718 cm⁻¹.

1-(3,4-Dichlorophenyl)-2,2,2-trifluoroethanol (AI5)

The product was isolated as a pale yellow liquid (500 mg, 65%): ¹H NMR(400 MHz, CDCl₃) δ 7.60 (s, 1H), 7.51 (m, 1H), 7.35 (m, 1H), 5.01 (m,1H), 2.60 (s, 1H); EIMS m/z 244 ([M]⁺).

1-(3,5-Dibromophenyl)-2,2,2-trifluoroethanol

The title molecule was isolated as a colorless liquid: ¹H NMR (300 MHz,CDCl₃) δ 7.67 (s, 1H), 7.58 (s, 2H), 5.08-5.02 (m, 1H), 4.42 (bs, 1H);EIMS m/z 333.7 ([M]⁺); IR (thin film) 3417, 2966, 1128, 531 cm⁻¹.

1-(4-Bromo-3,5-dichlorophenyl)-2,2,2-trifluoroethanol

The product was isolated as a colorless liquid: ¹H NMR (300 MHz,DMSO-d₆) δ 7.75 (s, 2H), 7.24 (d, J=6.0 Hz, 1H), 5.34-5.29 (m, 1H); EIMSm/z 321.88 ([M]⁺); IR (thin film) 3420, 1706, 1267, 804, 679 cm⁻¹.

1-(3,5-Dibromo-4-chlorophenyl)-2,2,2-trifluoroethanol

The product was isolated as a pale yellow gum: ¹H NMR (300 MHz, DMSO-d₆)δ 7.89 (s, 2H), 7.20 (d, J=6.0 Hz, 1H) 5.34-5.30 (m, 1H); EIMS m/z 366.0([M]⁺).

Step 2. 1-(1-Bromo-2,2,2-trifluoroethyl)-3,5-dichlorobenzene (AI1)

To a stirred solution of 1-(3,5-dichlorophenyl)-2,2,2-trifluoroethanol(4.0 g, 16.3 mmol) in CH₂Cl₂ (50 mL), were added N-bromosuccinimide(NBS; 2.9 g, 16.3 mmol) and triphenyl phosphite (5.06 g, 16.3 mmol), andthe resultant reaction mixture was heated at reflux for 18 h. After thereaction was deemed complete by TLC, the reaction mixture was cooled to25° C. and was concentrated under reduced pressure. Purification byflash column chromatography (SiO₂, 100-200 mesh; eluting with 100%pentane) afforded the title compound as a liquid (2.0 g, 40%): ¹H NMR(400 MHz, CDCl₃) δ 7.41 (s, 3H), 5.00 (m, 1H); EIMS m/z 306 ([M]⁺).

The following compounds were made in accordance with the proceduresdisclosed in Step 2 of Example 1.

5-(1-Bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (AI6)

The product was isolated as a colorless oil (300 mg, 60%): ¹H NMR (400MHz, CDCl₃) δ 7.59 (s, 2H), 5.00 (m, 1H); EIMS m/z 340.00 ([M]⁺).

5-(1-Bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-fluorobenzene (AI7)

The product was isolated as a colorless oil (320 mg, 60%): ¹H NMR (400MHz, CDCl₃) δ 7.45 (s, 2H), 5.00 (m, 2H); EIMS m/z 324.00 ([M]⁺).

4-(1-Bromo-2,2,2-trifluoroethyl)-1,2-dichlorobenzene (AI8)

The product was isolated as a colorless oil (300 mg, 60%): ¹H NMR (400MHz, CDCl₃) δ 7.63 (s, 1H), 7.51 (m, 1H), 7.35 (m, 1H), 5.01 (m, 1H);EIMS m/z 306.00 ([M]⁺).

1,3-Dibromo-5-(1-bromo-2,2,2-trifluoroethyl)benzene

The title molecule was isolated as a colorless liquid: ¹H NMR (300 MHz,CDCl₃) δ 7.71 (s, 1H), 7.59 (s, 2H), 5.04-4.97 (m, 1H); EIMS m/z 394.6([M]⁺); IR (thin film) 1114, 535 cm⁻¹.

2-Bromo-5-(1-bromo-2,2,2-trifluoroethyl)-1,3-dichlorobenzene

The title molecule was isolated as a colorless liquid: ¹H NMR (400 MHz,DMSO-d₆) δ 7.79 (s, 2H), 6.27-6.21 (m, 1H); EIMS m/z 383.9 ([M]⁺); IR(thin film) 2924, 1114, 749, 534 cm⁻¹.

1,3-Dibromo-5-(1-bromo-2,2,2-trifluoroethyl)-2-chlorobenzene

The title molecule was isolated as a pale yellow liquid: ¹H NMR (300MHz, DMSO-d₆) δ 7.97 (s, 2H), 6.27-6.19 (m, 1H); EIMS m/z 428.0 ([M]⁺).

Example 2 Preparation of N-Methyl-4-vinylbenzamide (AI9)

Step 1. 4-Vinylbenzoyl chloride (AI10)

To a stirred solution of 4-vinylbenzoic acid (1 g, 6.75 mmol) in CH₂Cl₂(20 mL) at 0° C. were added a catalytic amount of DMF and oxalylchloride (1.27 g, 10.12 mmol) dropwise over a period of 15 minutes(min). The reaction mixture was stirred at 25° C. for 6 h. After thereaction was deemed complete by TLC, the reaction mixture wasconcentrated under reduced pressure to give the crude acid chloride.

Step 2. N-Methyl-4-vinylbenzamide (AI9)

To 1 M N-methylamine in THF (13.5 mL, 13.5 mmol) at 0° C. were added TEA(1.34 mL, 10.12 mmol) and the acid chloride from Step 1 above in THF (10mL), and the reaction mixture was stirred at 25° C. for 3 h. After thereaction was deemed complete by TLC, the reaction mixture was quenchedwith water and then was extracted with EtOAc (3×). The combined EtOAclayer was washed with brine and dried over Na₂SO₄ and concentrated underreduced pressure to afford the title compound as an off-white solid (650mg, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.76 (d, J=8.0 Hz, 2H), 7.45 (d,J=8.0 Hz, 2H), 6.79 (m, 1H), 6.20 (br s, 1H), 5.82 (d, J=17.6 Hz, 1H),5.39 (d, J=10.8 Hz, 1H); ESIMS m/z 161.95 ([M+H]⁺).

The following compounds were made in accordance with the proceduresdisclosed in accordance with Example 2.

N,N-Dimethyl-4-vinylbenzamide (AI11)

The product was isolated as an off-white solid (650 mg, 60%): ¹H NMR(400 MHz, CDCl₃) δ 7.42 (m, 4H), 6.71 (m, 1H), 5.80 (d, J=17.6 Hz, 1H),5.31 (d, J=10.8 Hz, 1H), 3.05 (s, 3H), 3.00 (s, 3H); ESIMS m/z 176.01([M+H]⁺).

N-(2,2,3-Trifluoromethyl)-4-vinylbenzamide (AI12)

The product was isolated as an off-white solid (900 mg, 60%): ¹H NMR(400 MHz, CDCl₃) δ 7.76 (d, J=8.0 Hz, 2H), 7.45 (d, J=8.0 Hz, 2H), 6.79(m, 1H), 6.20 (br s, 1H), 5.82 (d, J=17.6 Hz, 1H), 5.39 (d, J=10.8 Hz,1H), 4.19 (m, 2H); ESIMS m/z 230.06 ([M+H]⁺).

Morpholino(4-vinylphenyl)methanone (AI13)

The product was isolated as a white solid (850 mg, 60%): ESIMS m/z218.12 ([M+H]⁺).

Example 3 Preparation of Ethyl 2-methyl-4-vinylbenzoate (AI14)

Step 1. 4-Formyl-2-methylbenzoic acid (AI15)

To a stirred solution of 4-bromo-2-methylbenzoic acid (10 g, 46.4 mmol)in dry THF (360 mL) at −78° C. was added n-BuLi (1.6 M solution inhexane; 58.17 mL, 93.0 mmol) and DMF (8 mL). The reaction mixture wasstirred at −78° C. for 1 h then was warmed to 25° C. and stirred for 1h. The reaction mixture was quenched with 1 N HCl solution and extractedwith EtOAc. The combined EtOAc extracts were washed with brine and driedover Na₂SO₄ and concentrated under reduced pressure. The residue waswashed with n-hexane to afford the title compound as a solid (3.0 g,40%): mp 196-198° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 13.32 (br s, 1H),10.05 (s, 1H), 7.98 (m, 1H), 7.84 (m, 2H), 2.61 (s, 3H); ESIMS m/z163.00 ([M−H]⁻).

Step 2. Ethyl 4-formyl-2-methylbenzoate (AI16)

To a stirred solution of 4-formyl-2-methylbenzoic acid (3 g, 18.2 mmol)in ethyl alcohol (EtOH; 30 mL) was added sulfuric acid (H₂SO₄, ×M; 2mL), and the reaction mixture was heated at 80° C. for 18 h. Thereaction mixture was cooled to 25° C. and concentrated under reducedpressure. The residue was diluted with EtOAc and washed with H₂O. Thecombined EtOAc extracts were washed with brine, dried over Na₂SO₄ andconcentrated under reduced pressure to afford the title compound as asolid (2.8 g, 80%): ¹H NMR (400 MHz, CDCl₃) δ 10.05 (s, 1H), 8.04 (m,1H), 7.75 (m, 2H), 4.43 (m, 2H), 2.65 (s, 3H), 1.42 (m, 3H).

Step 3. Ethyl 2-methyl-4-vinylbenzoate (AI14)

To a stirred solution of ethyl 4-formyl-2-methylbenzoate (2.8 g, 4 mmol)in 1,4-dioxane (20 mL) were added potassium carbonate (K₂CO₃; 3.01 g,21.87 mmol) and methyltriphenyl phosphonium bromide (7.8 g, 21.87 mmol)at 25° C. Then the reaction mixture was heated at 100° C. for 18 h.After the reaction was deemed complete by TLC, the reaction mixture wascooled to 25° C. and filtered, and the filtrate was concentrated underreduced pressure. The crude compound was purified by flashchromatography (SiO₂, 100-200 mesh; eluting with 25-30% EtOAc inn-Hexane) to afford the title compound as a solid (2.0 g, 72%): ¹H NMR(400 MHz, CDCl₃) δ 7.86 (m, 1H), 7.27 (m, 2H), 6.68 (dd, J=17.6, 10.8Hz, 1H), 5.84 (d, J=17.6 Hz, 1H), 5.39 (d, J=10.8 Hz, 1H), 4.39 (m, 2H),2.60 (s, 3H), 1.40 (m, 3H); ESIMS m/z 191.10 ([M−H]⁻); IR (thin film)2980, 1716, 1257 cm⁻¹.

Example 4 Preparation of tert-Butyl 2-chloro-4-vinylbenzoate (AI17)

Step 1. tert-Butyl 4-bromo-2-chlorobenzoate (AI18)

To a stirred solution of 4-bromo-2-chlorobenzoic acid (5 g, 21.37 mmol)in THF (30 mL) was added di-tert-butyl dicarbonate (25.5 g, 25.58 mmol),TEA (3.2 g, 31.98 mmol) and DMAP (0.78 g, 6.398 mmol), and the reactionmixture was stirred at 25° C. for 18 h. The reaction mixture was dilutedwith EtOAc and washed with H₂O. The combined organic layer was washedwith brine, dried over Na₂SO₄ and concentrated under reduced pressure.The residue was purified by flash chromatography (SiO₂, 100-200 mesh;eluting with 2-3% EtOAc in n-hexane) to afford the title compound as aliquid (3.2 g, 51%): ¹H NMR (400 MHz, CDCl₃) δ 7.62 (m, 2H), 7.44 (d,J=8.4 Hz, 1H), 1.59 (s, 9H); ESIMS m/z 290.10 ([M+H]⁺); IR (thin film)1728 cm⁻¹.

The following compounds were made in accordance with the proceduresdisclosed in Step 1 of Example 4.

tert-Butyl 2-bromo-4-iodobenzoate (AI19)

The product was isolated as a colorless oil (1.2 g, 50%): ¹H NMR (400MHz, CDCl₃) δ 8.01 (s, 1H), 7.68 (d, J=8.4 Hz, 1H), 7.41 (d, J=8.0 Hz,1H), 1.59 (s, 9H); ESIMS m/z 382.10 ([M+H]⁺); IR (thin film) 1727 cm⁻¹.

tert-Butyl 4-bromo-2-(trifluoromethyl)benzoate (AI20)

The product was isolated as a colorless oil (1 g, 52%): ¹H NMR (400 MHz,CDCl₃) δ 7.85 (s, 1H), 7.73 (d, J=8.4 Hz, 1H), 7.62 (d, J=8.4 Hz, 1H),1.57 (s, 9H); ESIMS m/z 324.10 ([M+H]⁺); IR (thin film) 1725 cm⁻¹.

Step 2. tert-Butyl 2-chloro-4-vinylbenzoate (AI17)

To a stirred solution of tert-butyl 4-bromo-2-chlorobenzoate (1.6 g,5.50 mmol) in toluene (20 mL) was addedtetrakis(triphenylphospine)palladium(0) (Pd(PPh₃)₄; (0.31 mg, 0.27mmol), K₂CO₃ (2.27 g, 16.5 mmol) and vinylboronic anhydride pyridinecomplex (2.0 g, 8.3 mmol) and the reaction mixture was heated to refluxfor 16 h. The reaction mixture was filtered, and the filtrate was washedwith H₂O and brine, dried over Na₂SO₄ and concentrated under reducedpressure. Purification by flash column chromatography (SiO₂, 100-200mesh; eluting with 5-6% EtOAc in n-hexane) afforded the title compoundas a liquid (0.6 g, 46%): ¹H NMR (400 MHz, CDCl₃) δ 7.72 (d, J=8.1 Hz,1H), 7.44 (m, 1H), 7.31 (d, J=8.0 Hz, 1H), 6.69 (dd, J=17.6, 10.8 Hz,1H), 5.85 (d, J=17.6 Hz, 1H), 5.40 (d, J=10.8 Hz, 1H), 1.60 (s, 9H);ESIMS m/z 238.95 ([M+H]⁺); IR (thin film) 2931, 1725, 1134 cm⁻¹.

The following compounds were made in accordance with the proceduresdisclosed in Step 2 of Example 4.

tert-Butyl 2-bromo-4-vinylbenzoate (AI21)

The product was isolated as a colorless oil (1 g, 52%): ¹H NMR (400 MHz,CDCl₃) δ 7.68 (m, 2H), 7.36 (d, J=8.0 Hz, 1H), 6.68 (dd, J=17.6, 10.8Hz, 1H), 5.84 (d, J=17.6 Hz, 1H), 5.39 (d, J=10.8 Hz, 1H), 1.60 (s, 9H);ESIMS m/z 282.10 ([M+H]⁺); IR (thin film) 2978, 1724, 1130 cm⁻¹.

tert-Butyl 2-(trifluoromethyl)-4-vinylbenzoate (AI22)

The product was isolated as a colorless oil (1.2 g, 50%): ¹H NMR (400MHz, CDCl₃) δ 7.71 (d, J=6.4 Hz, 2H), 7.59 (d, J=7.6 Hz, 1H), 6.77 (dd,J=17.6, 10.8 Hz, 1H), 5.89 (d, J=17.6 Hz, 1H), 5.44 (d, J=10.8 Hz, 1H),1.58 (s, 9H); ESIMS m/z 272.20 ([M+H]⁺); IR (thin film) 2982, 1727, 1159cm⁻¹.

Example 5 Preparation of tert-Butyl 2-cyano-4-vinylbenzoate (AI23)

To a stirred solution of tert-butyl 2-bromo-4-vinylbenzoate (0.5 g, 1.77mmol) in DMF (20 mL) was added copper(I) cyanide (CuCN; 0.23 g, 2.65mmol), and the reaction mixture was heated at 140° C. for 3 h. Thereaction mixture was cooled to 25° C., diluted with H₂O, and extractedwith EtOAc. The combined organic layer was washed with brine, dried overNa₂SO₄, and concentrated under reduced pressure. The residue waspurified by flash chromatography (SiO₂, 100-200 mesh; eluting with 15%EtOAc in n-hexane) to afford the title compound as a white solid (0.3 g,72%): mp 51-53° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.03 (s, 1H), 7.77 (s,1H), 7.64 (d, J=8.4 Hz, 1H), 6.75 (dd, J=17.6, 10.8 Hz, 1H), 5.93 (d,J=17.6 Hz, 1H), 5.51 (d, J=10.8 Hz, 1H), 1.65 (s, 9H); ESIMS m/z 229.84([M+H]⁺); IR (thin film) 2370, 1709, 1142 cm⁻¹.

Example 6 Preparation of Ethyl 2-bromo-4-iodobenzoate (AI46)

To a stirred solution of 4-iodo-2-bromobenzoic acid (5 g, 15.29 mmol) inethyl alcohol (EtOH; 100 mL) was added sulfuric acid (H₂SO₄; 5 mL), andthe reaction mixture was heated at 80° C. for 18 h. The reaction mixturewas cooled to 25° C. and concentrated under reduced pressure. Theresidue was diluted with EtOAc (2×100 mL) and washed with H₂O (100 mL).The combined EtOAc extracts were washed with brine, dried over Na₂SO₄and concentrated under reduced pressure to afford the compound as a paleyellow solid (5 g, 92%): ¹H NMR (400 MHz, DMSO-d₆) δ 8.04 (d, J=1.2 Hz,1H), 7.71 (d, J=7.6 Hz, 1H), 7.51 (d, J=8.4 Hz, 1H), 4.41 (q, J=7.2 Hz,2H), 1.41 (t, J=7.2 Hz, 3H).

The following compounds were made in accordance with the proceduresdisclosed in Example 6.

Ethyl 4-bromo-2-chlorobenzoate (AI47)

The title compound was isolated as an off-white solid (2.0 g, 80%): ¹HNMR (400 MHz, DMSO-d₆) δ 8.25 (d, J=1.2 Hz, 1H), 7.79 (d, J=7.6 Hz, 1H),7.65 (d, J=8.4 Hz, 1H), 4.65 (q, J=7.2 Hz, 2H), 1.56 (t, J=7.2 Hz, 3H).

Ethyl 4-bromo-2-methylbenzoate (AI48)

The title compound was isolated as a pale yellow liquid (3.0 g, 83%): ¹HNMR (400 MHz, CDCl₃) δ 7.79 (d, J=8.4 Hz, 1H), 7.41 (s, 1H), 7.39 (d,J=8.4 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 2.60 (s, 3H), 1.40 (t, J=7.2 Hz,3H) ESIMS m/z 229.11 ([M+H]⁺); IR (thin film) 1725 cm⁻¹.

Ethyl 4-bromo-2-fluorolbenzoate (AI49)

The title compound was isolated as a colorless liquid (9.0 g, 79%): ¹HNMR (400 MHz, DMSO-d₆) δ 7.84 (t, J=8.4 Hz, 1H), 7.76 (d, J=2.0 Hz, 1H),7.58 (d, J=1.6 Hz, 1H), 4.34 (q, J=7.2 Hz, 2H), 1.32 (t, J=7.2 Hz, 3H);ESIMS m/z 246.99 ([M+H]⁺), IR (thin film) 1734 cm⁻¹.

Example 7 Preparation of Ethyl 4-bromo-2-ethylbenzoate (AI50)

To a stirred solution of 4-bromo-2-fluorobenzoic acid (2.0 g, 9.17 mmol)in THF (16 mL), was added 1.0 Methyl magnesium bromide in THF (32 mL,32.0 mmol) dropwise at 0° C. and the resultant reaction mixture wasstirred at ambient temperature for 18 h. The reaction mixture wasquenched with 2 N HCl and extracted with ethyl acetate. The combinedethyl acetate layer was dried over anhydrous Na₂SO₄ and concentratedunder reduced pressure to afford crude 4-bromo-2-ethylbenzoic acid as acolorless liquid that was used in the next step without purification(0.4 g): ¹H NMR (400 MHz, CDCl₃) δ 7.64 (d, J=8.4 Hz, 1H), 7.47 (m, 1H),7.43 (m, 1H), 2.95 (q, J=4.0 Hz, 2H), 1.32 (t, J=4.0 Hz, 3H); ESIMS m/z228.97 ([M+H]⁺).

The title compound was synthesized from 4-bromo-2-ethylbenzoic acid inaccordance to the procedure in Example 6, isolated as a colorless liquid(0.15 g, 68%): ¹H NMR (400 MHz, DMSO-d₆) δ 7.90 (d, J=8.4 Hz, 1H), 7.47(m, 2H), 4.40 (q, J=7.2 Hz, 2H), 3.06 (q, J=7.6 Hz, 2H), 1.42 (t, J=7.2Hz, 3H), 1.26 (t, J=7.6 Hz, 3H); ESIMS m/z 226.96 ([M−H]⁻); IR (thinfilm) 3443, 1686, 568 cm⁻¹.

Example 8 Preparation of Ethyl 2-bromo-4-vinylbenzoate (AI51)

To a stirred solution of ethyl 2-bromo-4-iodobenzoate (5 g, 14.3 mmol)in THF/water (100 mL, 9:1) was added potassium vinyltrifluoroborate(1.89 g, 14.3 mmol), Cs₂CO₃ (18.27 g, 56.07 mmol) and triphenylphosphine(0.22 g, 0.85 mmol) and the reaction mixture was degassed with argon for20 min, then charged with PdCl₂ (0.05 g, 0.28 mmol). The reactionmixture was heated to reflux for 16 h. The reaction mixture was cooledto ambient temperature and filtered through a celite bed and washed withethyl acetate. The filtrate was again extracted with ethyl acetate andthe combined organic layers washed with water and brine, dried overNa₂SO₄ and concentrated under reduced pressure to afford crude compound.The crude compound was purified by column chromatography (SiO₂, 100-200mesh; eluting with 2% ethyl acetate/petroleum ether) to afford the titlecompound as a light brown gummy material (2 g, 56%): ¹H NMR (400 MHz,CDCl₃) δ 7.78 (d, J=8.4 Hz, 1H), 7.71 (d, J=1.2 Hz, 1H), 7.51 (d, J=8.4Hz, 1H), 6.69 (dd, J=17.6, 10.8 Hz, 1H), 5.86 (d, J=17.6 Hz, 1H), 5.42(d, J=11.2 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 1.43 (t, J=3.6 Hz, 3H);ESIMS m/z 255.18 ([M+H]⁺); IR (thin film) 1729 cm⁻¹.

The following compounds were made in accordance with the proceduresdisclosed in Example 8.

Ethyl 2-methyl-4-vinylbenzoate (AI52)

The title compound was isolated as a colorless liquid (0.8 g, 80%): ¹HNMR (400 MHz, CDCl₃) δ 7.89 (d, J=8.4 Hz, 1H), 7.27 (m, 2H), 6.79 (dd,J=17.6, 10.8 Hz, 1H), 5.86 (d, J=17.6 Hz, 1H), 5.42 (d, J=11.2 Hz, 1H),4.42 (q, J=7.2 Hz, 2H), 2.60 (s, 3H), 1.43 (t, J=7.2 Hz, 3H); ESIMS m/z191.10 ([M+H]⁺); IR (thin film) 1717, 1257 cm⁻¹.

Ethyl 2-fluoro-4-vinylbenzoate (AI53)

The title compound was isolated as a pale yellow liquid (2.0 g, 50%): ¹HNMR (400 MHz, DMSO-d₆) δ 7.87 (t, J=8.0 Hz, 1H), 7.51 (d, J=16.0 Hz,1H), 7.48 (d, J=16.0 Hz, 1H), 6.82 (dd, J=17.6, 10.8 Hz, 1H), 6.09 (d,J=17.6 Hz, 1H), 5.50 (d, J=10.8 Hz, 1H), 4.35 (q, J=7.2 Hz, 2H), 1.35(t, J=7.2 Hz, 3H); ESIMS m/z 195.19 ([M+H]⁺); IR (thin film) 1728 cm⁻¹.

Example 9 Preparation of Ethyl 2-chloro-4-vinylbenzoate (AI54)

To a stirred solution of ethyl 2-chloro-4-bromobenzoate (2 g, 7.63 mmol)in dimethylsulfoxide (20 mL) was added potassium vinyltrifluoroborate(3.06 g, 22.9 mmol) and potassium carbonate (3.16 g, 22.9 mmol). Thereaction mixture was degassed with argon for 30 min.Bistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride(0.27 g, 0.38 mmol) was added and the reaction mixture was heated to 80°C. for 1 h. The reaction mixture was diluted with water (100 mL),extracted with ethyl acetate (2×50 mL), washed with brine, dried overNa₂SO₄ and concentrated under reduced pressure to obtain the compound asbrown gummy material (1.1 g, 69%): ¹H NMR (400 MHz, CDCl₃) δ 7.81 (d,J=8.4 Hz, 1H), 7.46 (s, 1H), 7.33 (d, J=8.4 Hz, 1H), 6.70 (dd, J=17.6,11.2 Hz, 1H), 5.87 (d, J=17.6 Hz, 1H), 5.42 (d, J=10.8 Hz, 1H), 4.41 (q,J=7.2 Hz, 2H), 1.43 (t, J=7.2 Hz, 3H); ESIMS m/z 211.22 ([M+H]⁺); IR(thin film) 1729, 886 cm⁻¹.

The following compounds were made in accordance with the proceduresdisclosed in Example 9.

Ethyl 2-ethyl-4-vinylbenzoate (AI55)

The title compound was isolated as a color less liquid (1.0 g, 66%): ¹HNMR (300 MHz, CDCl₃) δ 7.85 (m, 1H), 7.29 (m, 2H), 6.76 (d, J=10.8 Hz,1H), 5.86 (d, J=17.6 Hz, 1H), 5.36 (d, J=10.5 Hz, 1H), 4.41 (q, J=7.2Hz, 2H), 3.10 (q, J=7.2 Hz, 2H), 1.40 (t, J=7.2 Hz, 3H), 1.30 (t, J=7.2Hz, 3H); ESIMS m/z 205.26 ([M+H]⁺); IR (thin film) 1720, 1607, 1263cm⁻¹.

Methyl 2-methoxy-4-vinylbenzoate (AI56)

The title compound was isolated as a pale yellow liquid (1.2 g, 75%): ¹HNMR (400 MHz, CDCl₃) δ 7.79 (d, J=8.0 Hz, 1H), 7.04 (d, J=1.2 Hz, 1H),6.97 (s, 1H), 6.74 (dd, J=11.2, 11.2 Hz, 1H), 5.86 (d, J=17.6 Hz, 1H),5.39 (d, J=17.6 Hz, 1H) 3.93 (s, 3H), 3.91 (s, 3H). ESIMS m/z 193.18([M+H]⁺); IR (thin film) 1732 cm⁻¹.

Example 10 Preparation of (E)-Ethyl4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoate(AI24)

To a stirred solution of ethyl 2-methyl-4-vinylbenzoate (2.0 g, 10.5mmol) in 1,2-dichlorobenzene (25 mL) were added1-(1-bromo-2,2,2-trifluoroethyl)-3,5-dichlorobenzene (6.44 g, 21.0mmol), copper(I) chloride (CuCl; 208 mg, 21 mmol) and 2,2bipyridyl (0.65g, 4.1 mmol). The reaction mixture was degassed with argon for 30 minand then stirred at 180° C. for 24 h. After the reaction was deemedcomplete by TLC, the reaction mixture was cooled to 25° C. and filtered,and the filtrate was concentrated under reduced pressure. Purificationby flash chromatography (SiO₂, 100-200 mesh; eluting with 25-30% EtOAcin petroleum ether) afforded the title compound as a solid (1.7 g, 40%):¹H NMR (400 MHz, CDCl₃) δ 7.91 (d, J=8.0 Hz, 1H), 7.37 (m, 1H),7.27-7.24 (m, 4H), 6.59 (d, J=16.0 Hz, 1H), 6.59 (dd, J=16.0, 8.0 Hz,1H), 4.38 (q, J=7.2 Hz, 2H), 4.08 (m, 1H), 2.62 (s, 3H), 1.42 (t, J=7.2Hz, 3H); ESIMS m/z 415.06 ([M−H]⁻); IR (thin film) 1717, 1255, 1114cm⁻¹.

Compounds AI25, AI57-AI68 and AC1-AC5 (Table 1) were made in accordancewith the procedures disclosed in Example 10.

(E)-Ethyl4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)-benzoicacid (AI25)

The product was isolated as a pale brown gummy liquid (500 mg, 40%): ¹HNMR (400 MHz, CDCl₃) δ 7.79 (d, J=8.0 Hz, 1H), 7.71 (m, 1H), 7.61 (d,J=7.6 Hz, 1H), 7.42 (s, 2H), 6.70 (d, J=16.0 Hz, 1H), 6.57 (dd, J=16.0,8.0 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 4.19 (m, 1H), 1.40 (t, J=7.6 Hz,3H); ESIMS m/z 502.99 ([M−H]⁻); IR (thin film) 1730, 1201, 1120, 749cm⁻¹.

(E)-Ethyl4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-fluorobenzoate(AI57)

¹H NMR (400 MHz, CDCl₃) δ 7.38 (s, 1H), 7.26 (s, 3H), 7.21 (d, J=8.4 Hz,1H), 7.16 (d, J=11.6 Hz, 1H), 6.59 (d, J=16.0 Hz, 1H), 6.47 (dd,J=,16.0, 8.0 Hz, 1H), 4.41 (q, J=6.8 Hz, 2H), 4.18 (m, 1H), 1.41 (t,J=6.8 Hz, 3H); ESIMS m/z 419.33 ([M−H]⁻); IR (thin film) 1723, 1115, 802cm⁻¹.

(E)-Ethyl4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-bromobenzoate(AI58)

¹H NMR (400 MHz, CDCl₃) δ 7.79 (d, J=8.0 Hz, 1H), 7.67 (s, 1H), 7.38 (m,2H), 7.26 (m, 2H), 6.56 (d, J=16.0 Hz, 1H), 6.45 (dd, J=16.0, 7.6 Hz,1H), 4.42 (q, J=7.2 Hz, 2H), 4.39 (m, 1H), 1.42 (t, J=7.2 Hz, 3H); ESIMSm/z 481.22 ([M−H]⁻); IR (thin film) 1727, 1114, 801, 685 cm⁻¹.

(E)-Ethyl 2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoate (AI59)

¹H NMR (400 MHz, CDCl₃) δ 7.79 (d, J=8.0 Hz, 1H), 7.67 (d, J=1.6 Hz,1H), 7.40 (s, 2H), 7.36 (d, J=1.6 Hz, 1H), 6.56 (d, J=16.0 Hz, 1H), 6.44(dd, J=16.0, 7.6 Hz, 1H), 4.42 (q, J=6.8 Hz, 2H), 4.15 (m, 1H), 1.42 (t,J=6.8 Hz, 3H); ESIMS m/z 514.74 ([M−H]⁻); IR (thin film) 1726, 1115,808, 620 cm⁻¹.

(E)-Ethyl 2-methyl-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoate (AI60)

The title compound was isolated as a light brown gummy material: ¹H NMR(400 MHz, CDCl₃) δ 7.90 (d, J=8.8 Hz, 1H), 7.34 (d, J=6.0 Hz, 2H), 7.25(d, J=7.2 Hz, 2H), 6.59 (d, J=16.0 Hz, 1H), 6.42 (dd, J=16.0, 8.0 Hz,1H), 4.38 (q, J=7.2 Hz, 2H), 4.19 (m, 1H), 2.63 (s, 3H), 1.41 (t, J=7.2Hz, 3H).

(E)-Ethyl 2-chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoate (AI61)

¹H NMR (400 MHz, CDCl₃) δ 7.87 (d, J=8.0 Hz, 1H), 7.46 (d, J=1.6 Hz,1H), 7.40 (s, 2H), 7.31 (d, J=1.6 Hz, 1H), 6.57 (d, J=16.0 Hz, 1H), 6.44(dd, J=16.0 Hz, 8.0 Hz, 1H), 4.42 (q, J=6.8 Hz, 2H), 4.15 (m, 1H), 1.42(t, J=6.8 Hz, 3H); ESIMS m/z 470.73 ([M−H]⁻); IR (thin film) 1726, 1115,809, 3072 cm⁻¹.

(E)-Ethyl4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)benzoate(AI62)

The title compound was isolated as a pale brown liquid (1.0 g, 46.3%):¹H NMR (400 MHz, CDCl₃) δ 7.79 (d, J=8.0 Hz, 1H), 7.71 (s, 1H), 7.61 (d,J=7.6 Hz, 1H), 7.41 (s, 2H) 6.65 (d, J=16.0 Hz, 1H), 6.49 (dd, J=16.0,8.0 Hz, 1H), 4.42 (q, J=7.6 Hz, 2H), 4.15 (m, 1H), 1.42 (t, J=7.6 Hz,3H); ESIMS m/z 502.99 ([M−H]⁻); IR (thin film) 1730, 1202, 1120, 750cm⁻¹.

(E)-Ethyl2-chloro-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoate(AI63)

¹H NMR (400 MHz, CDCl₃) δ 7.85 (d, J=6.0 Hz, 1H), 7.46 (d, J=1.8 Hz,2H), 7.34 (m, 1H), 7.24 (m, 1H), 6.57 (d, J=16.2 Hz, 1H), 6.45 (dd,J=16.2, 7.2 Hz, 1H), 4.43 (q, J=7.2 Hz, 2H), 4.13 (m, 1H), 1.41 (t,J=7.2 Hz, 3H); ESIMS m/z 455.0 ([M+H]⁺); IR (thin film) 1728, 1115, 817cm⁻¹.

(E)-Ethyl2-fluoro-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoate(AI64)

¹H NMR (400 MHz, CDCl₃) δ 7.93 (t, J=7.6 Hz, 1H), 7.34 (d, J=5.6 Hz,2H), 7.21 (d, J=8.0 Hz, 1H), 7.16 (d, J=11.6 Hz, 1H), 6.59 (d, J=16.0Hz, 1H), 6.49 (dd, J=16.0, 7.6 Hz, 1H), 4.42 (q, J=7.6 Hz, 2H), 4.13 (m,1H), 1.41 (t, J=7.6 Hz, 3H); ESIMS m/z 436.81 ([M−H]⁻); IR (thin film)1725 cm⁻¹.

(E)-Ethyl2-bromo-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoate(AI65)

¹H NMR (400 MHz, CDCl₃) δ 7.94 (d, J=8.0 Hz, 1H), 7.67 (s, 1H), 7.36 (m,3H), 6.56 (d, J=15.6 Hz, 1H), 6.44 (dd, J=15.6, 8.0 Hz, 1H), 4.42 (q,J=6.8 Hz, 2H), 4.10 (m, 1H), 1.42 (t, J=6.8 Hz, 3H); ESIMS m/z 498.74([M−H]⁻); IR (thin film) 1726, 1114, 820, 623 cm⁻¹.

(E)-Ethyl2-methyl-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoate(AI66)

The title compound was isolated as a brown semi-solid: ¹H NMR (400 MHz,CDCl₃) δ 7.90 (d, J=8.8 Hz, 1H), 7.34 (d, J=6.0 Hz, 2H), 7.25 (d, J=7.2Hz, 2H), 6.59 (d, J=16.0 Hz, 1H), 6.42 (dd, J=16.0 Hz, 8.0 Hz, 1H), 4.38(q, J=7.2 Hz, 2H), 4.19 (m, 1H), 2.63 (s, 3H), 1.41 (t, J=7.2 Hz, 3H);ESIMS m/z 432.90 ([M−H]⁻); IR (thin film) 1715 cm⁻¹.

(E)-Methyl2-methoxy-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoate(AI67)

¹H NMR (400 MHz, CDCl₃) δ 7.80 (d, J=8.4 Hz, 1H), 7.35 (d, J=6.0 Hz,2H), 7.03 (d, J=1.2 Hz, 1H), 6.92 (s, 1H), 6.59 (d, J=15.6 Hz, 1H), 6.42(dd, J=15.6, 8.0 Hz, 1H), 4.13 (m, 1H), 3.93 (s, 3H), 3.88 (s, 3H);ESIMS m/z 437.29 ([M+H]⁺); IR (thin film) 1724 cm⁻¹.

(E)-Ethyl2-ethyl-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoate(AI68)

¹H NMR (400 MHz, CDCl₃) δ 7.85 (d, J=8.0 Hz, 1H), 7.35 (d, J=9.6 Hz,2H), 7.26 (m, 1H), 7.24 (m, 1H), 6.60 (d, J=15.6 Hz, 1H), 6.42 (dd,J=15.6, 8.0 Hz, 1H), 4.38 (q, J=7.2 Hz, 2H), 4.14 (m, 1H), 3.01 (q,J=7.6 Hz 2H), 1.41 (t, J=7.2 Hz, 3H), 1.26 (t, J=7.6 Hz, 3H); ESIMS m/z447.05 ([M−H]⁻); IR (thin film) 1715, 1115, 817 cm⁻¹.

Example 11 Preparation of(E)-4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoicacid (AI32)

To a stirred solution of (E)-ethyl4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoate(1.7 g, 4.0 mmol) in 1,4-dioxane (10 mL) was added 11 N HCl (30 mL), andthe reaction mixture was heated at 100° C. for 48 h. The reactionmixture was cooled to 25° C. and concentrated under reduced pressure.The residue was diluted with H₂O and extracted with chloroform (CHCl₃).The combined organic layer was dried over Na₂SO₄ and concentrated underreduced pressure, and the crude compound was washed with n-hexane toafford the title compound as a white solid (0.7 g, 50%): mp 142-143° C.;¹H NMR (400 MHz, DMSO-d₆) δ 12.62 (br s, 1H), 7.81 (d, J=8.0 Hz, 1H),7.66 (s, 3H), 7.52-7.44 (m, 2H), 6.89 (dd, J=16.0, 8.0 Hz, 1H),6.78-6.74 (d, J=16.0 Hz, 1H), 4.84 (m, 1H), 2.50 (s, 3H); ESIMS m/z387.05 ([M−H]⁻); IR (thin film) 3448, 1701, 1109, 777 cm⁻¹.

The following compounds were made in accordance with the proceduresdisclosed in Example 11.

(E)-2-Methyl-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoicacid (AI26)

The product was isolated as a pale brown gummy liquid (1 g, 46%): ¹H NMR(400 MHz, CDCl₃) δ 7.97 (d, J=8.0 Hz, 1H), 7.77 (s, 1H), 7.65 (m, 1H),7.41 (s, 2H), 6.68 (d, J=16.0 Hz, 1H), 6.53 (dd, J=16.0, 8.0 Hz, 1H),4.16 (m, 1H), 2.50 (s, 3H); ESIMS m/z 422.67 ([M−H]⁻).

(E)-2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoicacid (AI27)

The product was isolated as an off-white semi-solid (1 g, 45%): ¹H NMR(400 MHz, CDCl₃) δ 7.99 (d, J=8.4 Hz, 1H), 7.50 (m, 1H), 7.40 (s, 1H),7.36 (m, 2H), 6.59 (d, J=15.6 Hz, 1H), 6.48 (dd, J=15.6, 7.6 Hz, 1H),4.14 (m, 1H); ESIMS m/z 442.72 ([M−H]⁻); IR (thin film) 3472, 1704,1113, 808 cm⁻¹.

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoicacid (AI28)

The product was isolated as a brown solid (1 g, 45%): mp 70-71° C.; ¹HNMR (400 MHz, CDCl₃) δ 7.99 (d, J=8.0 Hz, 1H), 7.72 (s, 1H), 7.40 (m,3H), 6.58 (d, J=16.0 Hz, 1H), 6.48 (dd, J=16.0, 8.0 Hz, 1H), 4.14 (m,1H); ESIMS m/z 484.75 ([M−H]⁻); IR (thin film) 3468, 1700 cm⁻¹.

(E)-2-Cyano-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoicacid (AI29)

The product was isolated as an off-white solid (500 mg, 45%): mp100-101° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.90 (s, 1H), 7.85 (d, J=7.6 Hz,1H), 7.72 (d, J=8.0 Hz, 1H), 7.65 (br s, 1H), 7.42 (s, 2H), 6.73 (d,J=16.0 Hz, 1H), 6.58 (dd, J=16.0, 8.0 Hz, 1H), 4.19 (m, 1H); ESIMS m/z431.93 ([M−H]⁻).

E)-4-(3-(3,4-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoicacid (AI30)

The product was isolated as a pale brown liquid (500 mg, 46%): ¹H NMR(400 MHz, CDCl₃) δ 8.03 (m, 1H), 7.49 (m, 2H), 7.29 (m, 1H), 7.22 (m,2H), 6.73 (d, J=16.0 Hz, 1H), 6.58 (dd, J=16.0, 7.8 Hz, 1H), 4.16 (m,1H), 2.64 (s, 3H); ESIMS m/z 386.84 ([M−H]⁻); IR (thin film) 3428, 1690,1113, 780 cm⁻¹.

(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoicacid (AI31)

The product was isolated as a white solid (500 mg, 50%): mp 91-93° C.;¹H NMR (400 MHz, CDCl₃) δ 8.02 (d, J=8.0 Hz, 1H), 7.35 (d, J=5.6 Hz,1H), 7.30 (m, 3H), 6.61 (d, J=16.0 Hz, 1H), 6.48 (dd, J=16.0, 8.0 Hz,1H), 4.13 (m, 1H), 2.65 (s, 3H); ESIMS m/z 406.87 ([M−H]⁻).

(E)-4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)benzoicacid (AI33)

The product was isolated as a white solid (500 mg, 45%): mp 142-143° C.;¹H NMR (400 MHz, CDCl₃) δ 7.97 (d, J=8.0 Hz, 1H), 7.77 (s, 1H), 7.65 (m,1H), 7.41 (s, 2H), 6.68 (d, J=16.0 Hz, 1H), 6.53 (dd, J=16.0, 8.0 Hz,1H), 4.16 (m, 1H); ESIMS m/z 474.87 ([M−H]⁻).

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoicacid (AI69)

The title compound was isolated as a brown solid (0.8 g, 28%): ¹H NMR(400 MHz, CDCl₃) δ 13.42 (br, 1H), 7.98 (d, J=1.5 Hz, 1H), 7.94 (m, 2H),7.75 (d, J=8.1 Hz, 1H), 7.65 (m, 1H), 7.06 (dd, J=15.9, 9.0 Hz, 1H),6.80 (d, J=15.9 Hz, 1H), 4.91 (m, 1H); ESIMS m/z 484.75 ([M−H]⁻); IR(thin film) 3469, 1700 cm⁻¹.

(E)-2-Bromo-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoicacid (AI70)

The title compound was isolated as a yellow liquid (0.3 g, crude): ¹HNMR (300 MHz, CDCl₃) δ 7.79 (d, J=8.1 Hz, 1H), 7.67 (s, 1H), 7.34 (m,3H), 6.56 (d, J=15.9 Hz, 1H), 6.45 (dd, J=15.9, 7.6 Hz, 1H), 4.43 (m,1H); ESIMS m/z 471.0 ([M−H]⁻).

(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-ethylbenzoicacid (AI71)

The title compound was isolated as a brown gummy material (0.2 g,crude): ¹H NMR (300 MHz, DMSO-d₆) δ 12.5 (br, 1H), 7.85 (d, J=6.3 Hz,2H), 7.75 (d, J=8.1 Hz, 1H), 7.52 (m, 2H), 6.96 (dd, J=8.7, 8.7 Hz, 1H),6.78 (d, J=15.6 Hz, 1H), 4.80 (m, 1H), 4.06 (q, J=7.2 Hz, 2H), 1.33 (t,J=7.2 Hz, 3H); ESIMS m/z 419.06 ([M−H]⁻).

(E)-2-Chloro-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoicacid (AI72)

The title compound was isolated as a yellow liquid (0.7 g, 95%): ¹H NMR(300 MHz, CDCl₃) δ 7.85 (d, J=6.0 Hz, 1H), 7.46 (d, J=1.8 Hz, 1H), 7.41(s, 3H), 6.57 (d, J=16.0 Hz, 1H), 6.45 (dd, J=16.0, 8.0 Hz, 1H), 4.16(m, 1H); ESIMS m/z 455.0 ([M+H]⁺); IR (thin film) 1728, 1115, 817 cm⁻¹.

(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoicacid (AI73)

The title compound was isolated as a light brown gummy material (0.7 g,38%): mp 91-93° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.02 (d, J=8.0 Hz, 1H),7.35 (d, J=5.6 Hz, 1H), 7.30 (m, 3H), 6.10 (d, J=16.0 Hz, 1H), 6.46 (dd,J=16.0, 8.0 Hz, 1H), 4.03 (m, 1H), 2.65 (s, 3H); ESIMS m/z 406.87([M−H]⁻).

(E)-4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-fluorobenzoicacid (AI74)

The title compound was isolated as a light brown liquid (0.3 g, crude):ESIMS m/z 393.15 ([M−H]⁻).

(E)-2-Bromo-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)benzoicacid (AI75)

The title compound was isolated as a light brown liquid (0.35 g, crude):ESIMS m/z 451.91 ([M−H]⁻).

Prophetically, compounds AI34, AI36-AI41, AI44-AI45 (Table 1) could bemade in accordance with the procedures disclosed in Example 10, orExamples 10 and 11.

Example 12 Preparation of(E)-4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methyl-N-(2,2,2-trifluoroethyl)benzamide(AC6)

To a stirred solution of(E)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoicacid in DMF was added 2,2,2-trifluoroethylamine, 1-hydroxybenzotriazolehydrate (HOBt.H₂O), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimidehydrochloride (EDC.HCl) and DIPEA, and the reaction mixture was stirredat 25° C. for 18 h. The reaction mixture was diluted with H₂O andextracted with EtOAc. The combined organic layer was washed with brine,dried over Na₂SO₄ and concentrated under reduced pressure. Purificationby flash column chromatography (SiO₂, 100-200 mesh; eluting withhexane:EtOAc afforded a white semi-solid (110 mg, 50%): ¹H NMR (400 MHz,CDCl₃) 7.40 (m, 2H), 7.26 (m, 3H), 6.56 (d, J=16.0 Hz, 1H), 6.48 (dd,J=16.0, 8.0 Hz, 1H), 5.82 (br s, 1H), 4.08 (m, 3H), 2.52 (s, 3H); ESIMSm/z 468.40 ([M−H]⁻); IR (thin film) 1657, 1113, 804 cm⁻¹.

Compounds AC7-AC38, AC40-AC58, AC110-AC112, AC117, and AC118 (Table 1)were made in accordance with the procedures disclosed in Example 12.

Example 13 Preparation of4-((E)-3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methyl-N-((pyrimidin-5-yl)methyl)benzamide(AC39)

To a stirred solution of (pyrimidin-5-yl)methanamine (0.15 g, 1.43 mmol)in CH₂Cl₂ (10 mL) was added drop wise trimethylaluminum (2 M solution intoluene; 0.71 mL, 1.43 mmol), and the reaction mixture was stirred at25° C. for 30 min A solution of ethyl4-((E)-3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoate(0.3 g, 0.71 mmol) in CH₂Cl₂ was added drop wise to the reaction mixtureat 25° C. The reaction mixture was stirred at reflux for 18 h, cooled to25° C., quenched with 0.5 N HCl solution (50 mL) and extracted withEtOAc (2×50 mL). The combined organic extracts were washed with brine,dried over Na₂SO₄, and concentrated under reduced pressure. The crudecompound was purified by flash chromatography (SiO₂, 100-200 mesh;eluting with 40% EtOAc in n-hexane) to afford the title compound (0.18g, 55%): mp 141-144° C.;

¹H (400 MHz, CDCl₃) δ 9.19 (s, 1H), 8.79 (s, 2H), 7.37 (m, 2H), 7.23 (m,2H), 7.21 (m, 1H), 6.57 (d, J=16.0 Hz, 1H), 6.40 (dd, J=16.0, 7.6 Hz1H), 6.21 (m, 1H), 4.65 (s, 2H), 4.11 (m, 1H), 2.46 (s, 3H); ESIMS m/z477.83 ([M−H]⁻).

Example 14 Preparation of(E)-2-Chloro-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(AC64)

To a stirred solution of glycine amide (0.15 g, 0.58 mmol) in CH₂Cl₂ (5mL) was added trimethylaluminum (2 M solution in toluene; 1.45 mL, 2.91mmol) dropwise, and the reaction mixture was stirred at 28° C. for 30min A solution of (E)-ethyl2-chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoate(0.3 g, 0.58 mmol) in CH₂Cl₂ (5 mL) was added drop wise to the reactionmixture at 28° C. The reaction mixture was stirred at reflux for 18 h,cooled to 25° C., quenched with 1N HCl solution (50 mL) and extractedwith CH₂Cl₂ (2×50 mL). The combined organic extracts were washed withbrine, dried over Na₂SO₄, and concentrated under reduced pressure. Thecrude compound was purified by flash chromatography (SiO₂, 100-200 mesh;eluting with 40% EtOAc in n-hexane) to afford the title compound asyellow solid (0.15 g, 50%): mp 83-85° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.72(d, J=8.0 Hz, 1H), 7.44 (s, 1H), 7.40 (s, 2H), 7.36 (d, J=6.8 Hz, 1H),7.05 (t, J=5.2 Hz, 1H), 6.70 (t, J=5.2 Hz, 1H), 6.57 (d, J=15.6 Hz, 1H),6.44 (dd, J=15.6, 8.0 Hz, 1H), 4.23 (d, J=5.6 Hz, 2H), 4.15 (m, 1H),4.01 (m, 2H); ESIMS m/z 580.72 ([M−H]⁻).

Compounds AC59-AC75 (Table 1) were made in accordance with theprocedures disclosed in Example 14.

Example 15 Preparation of(E)-2-Bromo-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide(AC79)

To a stirred solution of(E)-2-bromo-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoicacid (300 mg, 0.638 mmol) in CH₂Cl₂ (5.0 mL) was added2-amino-N-(2,2,2-trifluoroethyl)acetamide (172. mg, 0.638 mmol) followedby benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate(PyBOP) (364.5 mg, 0.701 mmol) and DIPEA (0.32 mL, 1.914 mmol), and theresultant reaction mixture was stirred at ambient temperature for 18 h.The reaction mixture was diluted with water and extracted with CH₂Cl₂.The combined CH₂Cl₂ layer was washed with brine, dried over Na₂SO₄ andconcentrated under reduced pressure. Purification by flash columnchromatography (SiO₂, 100-200 mesh; eluting with 40% ethylacetate/petroleum ether) afforded the title compound as an off-whitesolid (121 mg, 31%): ¹H NMR (400 MHz, CDCl₃) δ 8.69 (t, J=6.0 Hz, 1H),8.58 (t, J=6.0 Hz, 1H), 7.92 (s, 1H), 7.87 (d, J=6.4 Hz, 2H), 7.62 (d,J=8.4 Hz, 1H), 7.45 (d, J=8.4 Hz, 1H), 7.0 (m, 1H), 6.76 (d, J=15.6 Hz,1H), 4.83 (t, J=8.0 Hz, 1H), 3.98 (m, 4H); ESIMS m/z 610.97 ([M+H]⁺); IR(thin film) 3303, 1658, 1166, 817 cm⁻¹.

Compounds AC76-AC80, AC96-AC102, and AC113 (Table 1) were made inaccordance with the procedures disclosed in Example 15.

Example 16 Preparation of(E)-4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N-(1,1-dioxidothietan-3-yl)-2-fluorobenzamide(AC83)

To a stirred solution of(E)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-fluoro-N-(thietan-3-yl)benzamide(100 mg, 0.2159 mmol) in acetone/water (1:1, 5.0 mL) was added oxone(266 mg, 0.4319 mmol) and the resultant reaction mixture was stirred atambient temperature for 4 h. The reaction mixture was diluted with waterand extracted with ethyl acetate. The combined ethyl acetate layer wasdried over anhydrous Na₂SO₄ and concentrated under reduced pressure.Purification by flash column chromatography (SiO₂, 100-200 mesh; elutingwith 30% ethyl acetate/pet ether) afforded the title compound as an offwhite solid (70.0 mg, 66%): ¹H NMR (400 MHz, CDCl₃) δ 8.07 (t, J=8.4 Hz,1H), 7.39 (t, J=1.6 Hz, 1H), 7.31 (d, J=1.2 Hz, 1H), 7.26 (m, 2H), 7.23(m, 2H), 7.19 (d, J=1.6 Hz, 1H), 6.60 (d, J=16.8 Hz, 1H), 6.49 (dd,J=16.8, 7.6 Hz, 1H), 4.90 (m, 1H), 4.64 (m, 2H), 4.14 (m, 2H); ESIMS m/z493.83 ([M−H]⁻); IR (thin film) 1527, 1113, 801, 1167, 1321 cm⁻¹.

Compounds AC81-AC87 (Table 1) were made in accordance with theprocedures disclosed in Example 16.

Example 17 Preparation of(E)-N-((5-Cyclopropyl-1,3,4-oxadiazol-2-yl)methyl)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-methylbenzamide(AC89)

A solution of(E)-N-(2-(2-(cyclopropanecarbonyl)hydrazinyl)-2-oxoethyl)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzamide(200 mg, 0.379 mmol) in POCl₃ (2.0 mL) was stirred at ambienttemperature for 10 min, then the resultant reaction mixture was heatedto 50° C. for 1 h. The reaction mixture was quenched with ice water at0° C. and extracted with ethyl acetate. The combined ethyl acetate layerwas washed with saturated NaHCO₃ solution and brine solution, dried overanhydrous Na₂SO₄, and concentrated under reduced pressure. Purificationby flash column chromatography (SiO₂, 100-200 mesh; eluting with 50%ethyl acetate/pet ether) afforded the title compound as a light browngummy material (70.0 mg, 36%): ¹H NMR (400 MHz, CDCl₃) δ 7.43 (m, 2H),7.27 (m, 2H), 7.23 (m, 2H), 6.58 (d, J=16.0 Hz, 1H), 6.41 (dd, J=16.0,7.6 Hz, 1H), 4.79 (d, J=5.6 Hz, 2H), 4.14 (m, 1H), 2.48 (s, 3H), 2.18(m, 1H), 1.16 (m, 4H); ESIMS m/z 509.89 ([M+H]⁺); IR (thin film) 1666,1166, 1112, 800 cm⁻¹.

Example 18 Preparation of(E)-2-Bromo-N-(2-thioxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzothioamide(AC90)

To a stirred solution of(E)-2-bromo-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(400 mg, 0.638 mmol) in 5 mL of THF at ambient temperature was added2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide(Lawesson's reagent) (336 mg, 0.830 mmol) in one portion. The resultingreaction mixture was stirred for 18 h. TLC showed the reaction was notcomplete, therefore additional Lawesson's reagent (168 mg, 0.415 mmol)was added and reaction stirred for 48 h. After the reaction was deemedcomplete by TLC, the reaction mixture was concentrated under reducedpressure. Purification by flash chromatography (SiO₂, 230-400 mesh;eluting with 20% EtOAc in hexanes) afforded the title compound as ayellow glassy oil (188 mg, 44.7%): ¹H NMR (400 MHz, CDCl₃) δ 8.34 (m,1H), 8.27 (m, 1H), 7.60 (d, J=1.6 Hz, 1H), 7.49 (d, J=8.0 Hz, 2H), 7.40(s, 2H), 7.36 (dd, J=8.2, 1.7 Hz, 1H), 6.53 (d, J=16.0 Hz, 1H), 6.38(dd, J=15.9, 7.9 Hz, 1H), 4.89 (d, J=8.4, 5.5 Hz, 2H), 4.48 (qd, J=9.0,6.0 Hz, 2H), 4.11 (m, 1H); ESIMS m/z 656.9 ([M−H]⁻).

Example 19 Preparation of(E)-2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenylthioamido)-N-(2,2,2-trifluoroethyl)acetamide(AC91)

To a stirred solution of(E)-2-bromo-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(400 mg, 0.638 mmol) in 5 mL of THF at ambient temperature was addedLawesson's reagent (64.5 mg, 0.160 mmol) in one portion. The resultingreaction mixture was stirred for 18 h, after which time, the reactionmixture was concentrated under reduced pressure. Purification by flashchromatography (SiO₂, 230-400 mesh; eluting with 20% EtOAc in hexanes)afforded the title compounds as a yellow oil (18.5 mg, 4.51%): ¹H NMR(400 MHz, CDCl₃) δ 8.18 (t, J=5.0 Hz, 1H), 7.58 (d, J=1.6 Hz, 1H), 7.47(d, J=8.0 Hz, 1H), 7.40 (s, 2H), 7.34 (dd, J=8.1, 1.6 Hz, 1H), 6.52 (m,2H), 6.37 (dd, J=15.9, 7.9 Hz, 1H), 4.54 (d, J=4.9 Hz, 2H), 4.12 (m,1H), 3.99 (qd, J=8.9, 6.5 Hz, 2H); ESIMS m/z 640.9 ([M−H]⁻).

The following compound was made in accordance with the proceduresdisclosed in Example 19.

(E)-2-Bromo-N-(2-thioxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(AC92)

The product was isolated as a colorless oil (17.9 mg, 4.36%): ¹H NMR(400 MHz, CDCl₃) δ 9.16 (d, J=6.1 Hz, 1H), 7.65 (d, J=1.6 Hz, 1H), 7.57(d, J=8.0 Hz, 1H), 7.41 (m, 3H), 7.21 (t, J=5.6 Hz, 1H), 6.55 (d, J=15.9Hz, 1H), 6.41 (dd, J=15.9, 7.8 Hz, 1H), 4.59 (d, J=5.6 Hz, 2H), 4.45(qd, J=9.0, 6.0 Hz, 2H), 4.12 (q, J=7.2 Hz, 1H); ESIMS m/z 640.9([M−H]⁻).

Example 106 Preparation of Ethyl (Z)2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoate(AI76)

The title compound was made in accordance with the procedure disclosedin Example 88 and was isolated as a yellow viscous oil (416 mg, 23%): ¹HNMR (400 MHz, CDCl₃) δ 7.80 (d, J=8.0 Hz, 1H), 7.40 (d, J=1.7 Hz, 1H),7.35 (s, 2H), 7.12 (dd, J=8.0, 1.7 Hz, 1H), 6.86 (d, J=11.4 Hz, 1H),6.23-5.91 (m, 1H), 4.42 (q, J=7.1 Hz, 2H), 4.33-4.10 (m, 1H), 1.42 (t,J=7.2 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −69.34 (d, J=8.3 Hz); EIMS m/z514.10 ([M]⁻); IR (thin film) 2983, 1727, 1247, 1204, 1116 cm⁻¹.

Example 107 Preparation of(Z)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoicacid (AI77)

To a stirred solution of (Z)-ethyl2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoate(360 mg, 0.70 mmol) in CH₃CN (1.0 mL) was added iodotrimethylsilane(0.28 mL, 2.8 mmol). The reaction mixture was heated to reflux for 20 h,allowed to cool to ambient temperature and partitioned between CH₂Cl₂and aq. 10% Na₂S₂O₃. Organic phase was washed once with aq. 10% Na₂S₂O₃and dried over MgSO₄ and concentrated in vacuo. Passing the materialthrough a silica plug with 10% EtOAc in hexanes, followed by 20% MeOH inCH₂Cl₂) as the eluting solvents afforded the title compound as a yellowfoam (143 mg, 42%): mp 54-64° C.; ¹H NMR (400 MHz, CDCl₃) δ 11.36 (s,1H), 7.99 (d, J=8.0 Hz, 1H), 7.43 (s, 1H), 7.30 (s, 2H), 7.14 (d, J=7.9Hz, 1H), 6.85 (d, J=11.4 Hz, 1H), 6.15 (t, J=10.9 Hz, 1H), 4.36-4.09 (m,1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −69.30.

Example 108 Preparation of(Z)-2-Bromo-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(AC95)

To a stirred solution of(Z)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoicacid (200 mg, 0.41 mmol) in anhydrous THF (5.0 mL) was added DCI (82 mg,0.51 mmol). The mixture was heated in a 50° C. oil bath for 1.5 h,treated with 2-amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride(109 mg, 0.057 mmol) and the resulting mixture heated to reflux for 8 h.After cooling to ambient temperature, the mixture was taken up in Et₂Oand washed twice with aq. 5% NaHSO₄ (2×) and once with sat. NaCl (1×).After dying over MgSO₄, concentration in vacuo and purification bymedium pressure chromatography on silica with EtOAc/Hexanes as theeluents, the title compound was obtained as a white foam (160 mg, 41%)mp 48-61° C.: ¹H NMR (400 MHz, CDCl₃) δ 7.58 (d, J=7.9 Hz, 1H),7.44-7.29 (m, 3H), 7.14 (dd, J=7.9, 1.6 Hz, 1H), 6.86 (d, J=11.4 Hz,1H), 6.76 (t, J=5.9 Hz, 1H), 6.59 (br s, 1H), 6.21-6.04 (m, 1H), 4.23(d, J=5.5 Hz, 1H), 3.98 (qd, J=9.0, 6.5 Hz, 2H); ¹⁹F NMR (376 MHz,CDCl₃) δ −69.31, −72.3; EIMS m/z 626.9 ([M+1]⁺).

Example 109a Preparation of(E)-2-Bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(AC114)

(E)-tert-Butyl4-(2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamido)piperidine-1-carboxylate(0.75 g, 1.11 mmol) was added to dioxane HCl (10 mL) at 0° C. and wasstirred for 18 h. The reaction mixture was concentrated under reducedpressure and triturated with diethylether to afford the compound as alight brown solid (0.6 g, 88%).

Example 109b Preparation of(E)-N-(1-Acetylpiperidin-4-yl)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(AC103)

To a stirred solution of(E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamide(0.1 g, 0.16 mmol) in CH₂Cl₂ (10.0 mL) was added TEA (0.046 mL, 0.35mmol) and stirred for 10 min. Then acetyl chloride (0.014, 0.18 mmol)was added and stirred for 16 h at ambient temperature. The reactionmixture was diluted with CH₂Cl₂ and washed with saturated NaHCO₃solution and brine solution. The combined CH₂Cl₂ layer was dried overNa₂SO₄ and concentrated under reduced pressure to afford crude compound.The crude compound was washed with 5% diethyl ether/n-pentane to affordthe title compound as a white solid (0.054 g, 50%).

Example 110 Preparation of(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N-(1-(3,3,3-trifluoropropanoyl)piperidin-4-yl)benzamide(AC104)

To a stirred solution of 3,3,3-trifluoropropanoic acid (0.02 g, 0.16mmol) in CH₂Cl₂ (10.0 mL),(E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamide(0.1 g, 0.16 mmol), PYBOP (0.09 g, 0.17 mmol), and DIPEA (0.06 g, 0.48mmol) were added at ambient temperature. The reaction mixture wasstirred at ambient temperature for 5 h. The reaction mixture was dilutedwith CH₂Cl₂. The combined CH₂Cl₂ layer was washed with 3N HCl andsaturated NaHCO₃ solution, the separated CH₂Cl₂ layer was dried overanhydrous Na₂SO₄ and concentrated under reduced pressure to afford crudecompound. The crude compound was purified by column chromatography(SiO₂, 100-200 mesh; eluting with 2% MeOH in CH₂Cl₂) to afford the titlecompound as an off white gummy material (0.035 g, 29.%).

Example 111 Preparation of(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)benzamide(AC105)

To a stirred solution of(E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamide(0.1 g, 0.16 mmol) in THF (5.0 mL) was added TEA (0.06 mL, 0.64 mmol)and stirred for 10 min. Then 2,2,2-trifluoroethyltriflluoromethanesulfonate (0.03, 0.16 mmol) was added and stirred for16 h at ambient temperature. The reaction mixture was diluted with ethylacetate and washed with saturated NaHCO₃ solution and brine solution.The combined ethyl acetate layer was dried over Na₂SO₄ and concentratedunder reduced pressure to afford the title compound as a brown solid(0.05 g, 44%).

Example 112 Preparation of(E)-2-Bromo-N-(1-methylpiperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(AC106)

A solution of(E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamide(0.1 g, 0.16 mmol), formaldehyde (30% in water) (0.1 mL, 0.16 mmol) andacetic acid (0.01 mL) in MeOH (5.0 mL) was stirred at ambienttemperature for 30 min. After that NaBH₃CN (0.01 g, 0.16 mmol) was addedat 0° C. and the reaction was stirred for 8 h at ambient temperature.The solvent was removed under reduced pressure to obtain residue whichwas diluted with ethyl acetate and washed with saturated aq. NaHCO₃solution and brine solution. The combined ethyl acetate layer was driedover Na₂SO₄ and concentrated under reduced pressure to obtain a residue,which was triturated with diethyl ether/pentane to afford the titlecompound as a pale yellow gummy material (0.06 g, 59%).

Example 113 Preparation of((E)-2-Bromo-N-(1-(cyanomethyl)piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(AC107)

To a stirred solution of(E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamide(0.25 g, 0.43 mmol) in THF (10.0 mL) was added TEA (0.16 mL, 1.29 mmol)and the reaction was stirred for 10 min. Then 2-bromoacetonitrile

(0.07, 0.65 mmol) was added and the reaction was stirred for 8 h atambient temperature. The reaction mixture was diluted with ethyl acetateand washed with saturated brine solution. The combined ethyl acetatelayer was dried over Na₂SO₄ and concentrated under reduced pressure toafford the title compound as an off-white solid (0.125 g, 46.8%).

Example 114 Preparation of(E)-2-Bromo-N-(1-(oxetan-3-yl)piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(AC108)

A solution of(E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamide(0.2 g, 0.35 mmol), oxetan-3-one (0.027 g, 0.38 mmol) and acetic acid(0.01 mL) in MeOH (5.0 mL) was stirred at ambient temperature for 30min. After that NaBH₃CN (0.022 g, 0.35 mmol) was added at 0° C. slowlylot wise over the period of 10 min and the reaction was stirred for 8 hat ambient temperature. The solvent was removed under reduced pressureto obtain a residue which was diluted with ethyl acetate and washed withsaturated NaHCO₃ solution and brine solution. The combined ethyl acetatelayer was dried over Na₂SO₄ and concentrated under reduced pressure toobtain a residue, which was triturated with diethyl ether/pentane toafford the title compound as an off-white solid (0.05 g, 23%).

Example 115 Preparation of(E)-2-Bromo-N-(1-(2-hydroxyethyl)piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide(AC109)

To a stirred solution of(E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamide(0.25 g, 0.43 mmol) in THF (10.0 mL) was added TEA (0.16 mL, 1.29 mmol)and the reaction was stirred for 10 min. Then 2-chloroethanol (0.05,0.65 mmol) was added and the reaction was stirred for 8 h at ambienttemperature. The reaction mixture was diluted with ethyl acetate andwashed with saturated brine solution. The combined ethyl acetate layerwas dried over Na₂SO₄ and concentrated under reduced pressure to affordthe title compound as an off-white solid (0.09 g, 34%).

Example 116 Preparation of(E)-2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamido)aceticacid (AI78)

To a stirred solution of (E)-tert-butyl2-(2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamido)acetate(440 mg, 0.734 mmol) in CH₂Cl₂ (36.0 ml), was added TFA (4.0 mL) and thereaction mixture was stirred at ambient temperature for 1 h. Thereaction mixture was concentrated under reduced pressure to obtainresidue which was washed with n-pentane to afford the title compound asan off-white solid (310 mg, 78%): ¹H NMR (400 MHz, CDCl₃) δ 13.0 (s,1H), 8.75 (t, J=5.7 Hz, 1H), 7.93 (m, 2H), 7.62 (d, J=7.5 Hz, 1H), 7.40(d, J=8.1 Hz, 1H), 6.96 (dd, J=15.3, 9.3 Hz, 1H), 6.78 (d, J=15.3 Hz,1H), 4.83 (m, 1H), 3.90 (d, J=5.7 Hz, 2H); ESIMS m/z 543.61 ([M+H]⁺); IR(thin film) 3429, 1635, 1114, 772 cm⁻¹.

Example 117 Preparation of(E)-N-((6-Chloropyridin-3-yl)methyl)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-methylbenzothioamide(AC115)

To the stirred solution of(E)-N-((6-chloropyridin-3-yl)methyl)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzamide(0.06 g, 0.117 mmol) in toluene (3 mL) was added Lawesson's reagent(0.14 g, 0.351 mmol) and the reaction was irradiated at 100° C. for 1 h,then cooled to ambient temperature and concentrated under reducedpressure to provide crude compound. The crude product was purified bypreparative HPLC to afford the product as yellow color solid (0.03 g,49%).

Example 118 Preparation of(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethoxy)benzamide(AC116)

Step 1. 2-(Trifluoromethoxy)-4-vinylbenzoic acid (AI79)

To a stirred solution of 4-bromo-2-(trifluoromethoxy)benzoic acid (1 g,3.67 mmol) in DMSO (20 mL) was added potassium vinyltrifluoroborate(1.47 g, 11.02 mmol) and potassium carbonate (1.52 g, 11.02 mmol). Thereaction mixture was degassed with argon for 30 minBistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride(0.13 g, 0.18 mmol) was added and the reaction mixture was heated to 80°C. for 1 h. The reaction mixture was diluted with water (100 mL),extracted with ethyl acetate (2×50 mL), washed with brine, and driedover Na₂SO₄. Concentration under reduced pressure furnished the crudecompound which was purified by flash column chromatography to afford theproduct as pale yellow gummy material (0.4 g, 47%): ¹H NMR (400 MHz,CDCl₃) δ 8.05 (d, J=8.1 Hz, 1H), 7.44 (d, J=1.8 Hz, 1H), 7.35 (s, 1H),6.78 (dd, J=17.4.1, 11.1 Hz, 1H), 5.92 (d, J=17.4 Hz, 1H), 5.51 (d,J=10.8 Hz, 1H); ESIMS m/z 232.97 ([M+H]⁺).

Step 2.(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-(trifluoromethoxy)benzoicacid (AI80)

To a stirred solution of 2-(trifluoromethoxy)-4-vinylbenzoic acid (0.356g, 1.53 mmol) in 1N methylpyrrolidine (5.0 mL) was added1-(1-bromo-2,2,2-trifluoroethyl)-3,5-dichloro 4-fluorobenzene (1.0 g,3.07 mmol), copper(I) chloride (CuCl; 0.03 g, 0.307 mmol) and 2,2bipyridyl (0.095 g, 0.614 mmol). The reaction mixture was stirred at150° C. for 1 h. After the reaction was complete by TLC, the reactionmixture was diluted with water (100 mL) and extracted with ethyl acetate(2×50 mL). The combined organic layers were washed with brine, driedover Na₂SO₄ and concentrated under reduced pressure to obtain the crudecompound which was purified by flash column chromatography to afford theproduct as pale yellow gummy material (0.3 g, 21%): ¹H NMR (400 MHz,CDCl₃) δ 8.08 (d, J=8.0 Hz, 1H), 7.45 (d, J=1.6 Hz, 1H), 7.35 (s, 3H),6.63 (d, J=16.0 Hz, 1H), 6.50 (dd, J=16.0, 8.0 Hz, 1H), 4.15 (m, 1H);ESIMS m/z 474.81 ([M−H]⁻).

Step 3.(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)-2-(trifluoromethoxy)benzamide(AC116)

A mixture of(E)-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-(trifluoromethoxy)benzoicacid (0.25 g, 0.52 mmol), 2-amino-N-(2,2,2-trifluoroethyl)acetamide(0.158 g, 0.62 mmol), PyBOP (0.40 g, 0.78 mmol) and DIPEA (0.134 g, 1.04mmol) in CH₂Cl₂ (10.0 mL) were stirred at ambient temperature for 16 h.The reaction mixture was diluted with water and extracted with CH₂Cl₂.The combined CH₂Cl₂ layer was washed with brine, dried over Na₂SO₄ andconcentrated under reduced pressure. Purification by flash columnchromatography (SiO₂, 100-200 mesh; eluting with 20% ethyl acetate/petether) afforded the title compound as a pale yellow gummy material (0.15g, 47%).

The following molecules were made in accordance with the proceduresdisclosed in Example 118, Step 2:(E)-4-(3-(3,5-Dibromophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid

The title molecule was isolated as a brown solid: ¹H NMR (300 MHz,DMSO-d₆) δ 13.5 (bs, 1H), 8.03 (s, 1H), 7.95-7.85 (m, 4H), 7.81 (d,J=7.8 Hz, 1H), 7.14 (dd, J=15.6, 9.6 Hz, 1H), 6.90 (d, J=15.9 Hz, 1H),4.86-4.79 (m, 1H); ESIMS m/z 528.82 ([M−H]⁻); IR (thin film) 3437, 1707,1153, 555 cm⁻¹.

(E)-4-(3-(3,5-Dibromo-4-chlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid

Isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d6) δ, 13.36 (bs, 1H)8.05 (s, 2H), 7.95 (d, J=8.1 Hz, 1H), 7.87-7.67 (m, 2H), 7.14 (dd,J=9.0, 15.6 Hz, 1H), 6.96 (d, J=15.6 Hz, 1H), 4.88-4.82 (m, 1H); ESIMSm/z 564.58 ([M+H]⁺).

(E)-4-(3-(4-Bromo-3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid

Isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.6 (bs, 1H) 8.03(s, 1H), 7.95 (d, J=8.4 Hz, 1H), 7.88 (s, 2H), 7.81 (d, J=8.1 Hz, 1H),7.13 (dd, J=16.2, 7.5 Hz, 1H), 6.91 (d, J=15.9 Hz, 1H), 4.89-4.83 (m,1H); ESIMS m/z 532.0 ([M+H]⁺).

(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoicacid

The title molecule was isolated as an off white solid: mp 140-143° C.;¹H NMR (400 MHz, DMSO) δ 13.60 (bs, 1H), 8.02 (s, 1H), 7.94-7.90 (m,1H), 7.88-7.86 (m, 2H), 7.81-7.79 (m, 1H), 7.12 (dd, J=15.6, 8.8 Hz,1H), 6.89 (d, J=15.6 Hz, 1H), 4.86-4.81 (m, 2H); ESIMS m/z 458.88([M−H]⁻).

Example 20 Preparation of 5-Vinyl-2,3-dihydro-1H-inden-1-one (BI1)

To a stirred solution of 5-bromo-2,3-dihydro-1H-inden-1-one (5 g, 23.7mmol) in toluene were added vinylboronic anhydride pyridine complex(8.55 g, 35.54 mmol), Pd(PPh₃)₄ (0.1 g, 0.094 mmol), K₂CO₃ (22.88 g,165.83 mmol). The resultant reaction mixture was heated at reflux for 16h. The reaction mixture was cooled to 25° C. and filtered, and thefiltrate was concentrated under reduced pressure. The residue wasdiluted with EtOAc and washed with H₂O and brine. The combined organicextracts were dried over anhydrous Na₂SO₄ and concentrated under reducedpressure. The obtained residue was purified by flash columnchromatography (SiO₂, 5% EtOAc in petroleum ether) afforded the titlecompound as a solid (1.8 g, 48%): ¹H NMR (400 MHz, CDCl₃) δ 7.74 (d,J=7.2 Hz, 1H), 7.49 (br s, 1H), 7.44 (d, J=7.2 Hz, 1H), 6.82 (m, 1H),5.90 (d, J=7.4 Hz, 1H), 5.42 (d, J=6.4 Hz, 1H), 3.20 (m, 2H), 2.70 (m,2H); ESIMS m/z 159.06 ([M+H]⁻).

The following compound was made in accordance with the proceduresdisclosed in Example 20.

6-Vinyl-3,4-dihydronaphthalen-1(2H)-one (BI2)

The product was isolated as an off-white solid (5 g, 48%): ¹H NMR (400MHz, DMSO-d₆) δ 7.85 (d, J=8.4 Hz, 1H), 7.48 (m, 2H), 6.82 (m, 1H), 6.02(d, J=7.4 Hz, 1H), 5.44 (d, J=6.4 Hz, 1H), 2.95 (m, 2H), 2.60 (m, 2H),2.00 (m, 2H); ESIMS m/z 173.14 ([M−H]⁻); IR (thin film) 1681 cm⁻¹.

Example 21 Preparation of(E)-5-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1H-inden-1-one(BI3)

5-(1-Bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (4 g, 11.7mmol), 5-vinyl-2,3-dihydro-1H-inden-1-one (0.92 g, 5.8 mmol), CuCl(0.115 g, 1.171 mmol) and 2,2-bipyridyl (0.053 g, 0.34 mmol) in1,2-dichlorobenzene (25 mL) were heated at 180° C. for 16 h. Thereaction mixture was cooled to 25° C. and concentrated under reducedpressure. The residue was purified by flash column chromatography (SiO₂,5% EtOAc in petroleum ether) to afford the title compound as a liquid(1.28 g, 25%): ¹H NMR (400 MHz, CDCl₃) δ 7.76 (d, J=7.4 Hz, 1H), 7.52(m, 3H), 6.68 (d, J=7.4 Hz, 1H), 6.52 (m, 1H), 4.18 (m, 1H), 3.18 (m,2H), 2.75 (m, 2H); ESIMS m/z 419.14 ([M+H]⁻); IR (thin film) 1708.94,1113.60, 807.77 cm⁻¹.

The following compound was made in accordance with the proceduresdisclosed in Example 21.

(E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2,3-dihydro-1H-inden-1-one(BI4)

The product was isolated as a brown semi-solid (1.2 g, 16%): ¹H NMR (400MHz, CDCl₃) δ 7.76 (d, J=7.4 Hz, 1H), 7.54 (m, 3H), 7.30 (s, 1H), 6.68(d, J=7.4 Hz, 1H), 6.52 (m, 1H), 4.18 (m, 1H), 3.18 (m, 2H), 2.75 (m,2H); ESIMS m/z 400.84 ([M−H]⁻); IR (thin film) 815, 1113, 1709 cm⁻¹.

(E)-6-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-3,4-dihydronaphthalen-1(2H)-one(BI5)

The product was isolated as a pale yellow semi solid (1.2 g, 30%): ¹HNMR (400 MHz, CDCl₃) δ 8.20 (d, J=8.0 Hz, 1H), 7.42 (s, 2H), 7.35 (m,1H), 7.24 (m, 2H), 6.62 (d, J=16 Hz, 1H), 6.46 (m, 1H), 4.18 (m, 1H),2.95 (m, 2H), 2.65 (m, 2H), 2.19 (m, 2H); ESIMS m/z 432.94 ([M−H]⁻); IR(thin film) 1680, 1113, 808 cm⁻¹.

Example 22 Preparation of(E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-fluoro-2,3-dihydro-1H-inden-1-one(BI6)

To a stirred solution of(E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2,3-dihydro-1H-inden-1-one(0.5 g, 1.24 mmol) in acetonitrile (20 mL), was added Selectfluor® (0.52g, 1.48 mmol) and the reaction was heated to reflux temperature for 16h. The reaction mixture was cooled to room temperature, concentratedunder reduced pressure and diluted with CH₂Cl₂. The solution was washedwith water and brine, dried over anhydrous sodium sulfate andconcentrated under reduced pressure to give the crude product which waspurified by flash column chromatography (SiO₂, 100-200 mesh; 15% EtOAcin petroleum ether) to afford the title compound as a pale yellow semisolid (0.1 g, 24%): ¹H NMR (400 MHz, CDCl₃) δ 7.80 (m, 1H), 7.48 (m,2H), 7.32 (m, 2H), 6.65 (d, J=16.0 Hz, 1H), 6.54 (dd, J=16.0, 8.0 Hz,1H), 5.38 (m, 1H), 4.18 (m, 1H), 3.62 (m, 1H), 3.32 (m, 1H); ESIMS m/z419.06 ([M−H]⁻); IR (thin film) 1728, 1114, 817 cm⁻¹.

Example 23 Preparation of(E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N-(3,3,3-trifluoropropyl)-2,3-dihydro-1H-inden-1-amine(BC10)

To a stirred solution of(E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2,3-dihydro-1H-inden-1-one(0.15 g, 0.35 mmol) in DCE (10 mL), was added trifluoropropyl amine(0.048 g, 0.42 mmol) and sodium cyanoborohydride (0.055 g, 0.875 mmol)in cooling and the reaction mixture was stirred at room temperature for16 h. The reaction mixture was diluted with DCE, was washed with waterand brine and dried over anhydrous sodium sulfate. Concentration underreduced pressure gave the crude compound, which was purified by flashcolumn chromatography (SiO₂, 100-200 mesh; 10-15% EtOAc in petroleumether) to afford the title compound as a colorless gummy material (0.042g, 24%): ¹H NMR (400 MHz, CDCl₃) δ 7.38-7.20 (m, 5H), 6.62 (d, J=16.0Hz, 1H), 6.34 (dd, J=16.0, 8.0 Hz, 1H), 5.83 (br, 1H), 5.52 (m, 1H),4.12 (m, 1H), 3.02 (m, 3H), 2.82 (m, 1H), 2.50 (m, 2H), 1.82 (m, 1H),1.42 (m, 1H); ESIMS m/z 497.98 ([M−H]⁻); IR (thin film) 3027, 1654, 815cm⁻¹.

Example 24 Preparation of6-((E)-4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-3,4-dihydronaphthalen-1(2H)-oneoxime (BI5a)

To a stirred solution of((E)-6-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-3,4-dihydronaphthalen-1(2H)-one(0.4 g, 0.92 mmol) in EtOH (50 mL) were added hydroxylaminehydrochloride (0.128 g, 1.85 mmol) and sodium acetate (0.23 g, 2.77mmol), and the reaction mixture was heated at reflux for 3 h. Thereaction mixture was concentrated under reduced pressure, and theresidue was diluted with H₂O and extracted with EtOAc. The combinedorganic extracts were washed with brine, dried over anhydrous Na₂SO₄ andconcentrated under reduced pressure to give the crude compound, whichwas purified by flash column chromatography (SiO₂, 100-200 mesh; 10-15%EtOAc in petroleum ether). The title compound was isolated as a solid(0.3 g, 73%): mp 155-158° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.89 (d, J=8.4Hz, 1H), 7.41 (s, 2H), 7.24 (m, 1H), 7.17 (m, 1H), 6.57 (d, J=16 Hz,1H), 6.46 (dd, J=16.0, 8.0 Hz, 1H), 4.13 (m, 1H), 2.82 (m, 4H), 2.04 (m,2H); ESIMS m/z 445.95 ([M−H]⁻).

Example 25 Preparation of(E)-5-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1H-inden-1-amine(BI5b)

To a stirred solution of(E)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1H-inden-1-one(1 g, 2.39 mmol) in MeOH (10 mL) were added ammonium acetate (1.84 g,23.9 mmol) and sodium cyanoborohydride (NaCNBH₃; 0.44 g, 7.17 mmol,) andthe reaction mixture was heated at reflux for 16 h. The reaction mixturewas concentrated under reduced pressure, and the residue was dilutedwith H₂O and extracted with EtOAc. The combined organic extracts werewashed with H₂O and saturated aqueous sodium bicarbonate (satd aqNaHCO₃) solution, dried over anhydrous Na₂SO₄, and concentrated underreduced pressure to afford the title compound as a liquid (500 mg,crude): ¹H NMR (400 MHz, DMSO-d₆) δ 7.85 (s, 2H), 7.40 (s, 1H), 7.30 (s,2H), 6.71 (s, 2H), 4.78 (m, 1H), 4.2 (m, 1H), 2.80 (m, 1H), 2.73 (m,1H), 1.60 (m, 2H); ESIMS m/z 419.02 ([M+H]⁺); IR (thin film) 2924, 1552,1112, 807 cm⁻¹.

The following compound was made in accordance with the proceduresdisclosed in Example 25.

(E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2,3-dihydro-1H-inden-1-amine(BI7)

The product was isolated as a light brown gummy material, taken as suchto the next step (0.15 g, crude compound): ESIMS m/z 401.97 ([M−H]⁻).

(E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-fluoro-2,3-dihydro-1H-inden-1-amine(BI8)

The product was isolated as a light brown gummy material, taken as suchto the next step (0.15 g, crude compound): ESIMS m/z 420.15 ([M−H]⁻).

(E)-6-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-1,2,3,4-tetrahydronaphthalen-1-amine(BI9)

The product was isolated as a pale yellow liquid (500 mg crude).

Example 26 Preparation of(E)-1-Methyl-3-(5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)-but-1-enyl)-2,3-dihydro-1H-inden-1-yl)thiourea(BC1)

To a stirred solution of(E)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1H-inden-1-amine(0.1 g, 0.23 mmol) in Et₂O (5 mL) was added methylisothiocyanate (0.026g, 0.35 mmol), and the mixture was stirred for 2 h at 25° C. Thereaction mixture was concentrated under reduced pressure, and theresidue was purified by flash column chromatography (SiO₂, 20% EtOAc inpetroleum ether). The title compound was isolated as a liquid (65 mg,50%): ¹H NMR (400 MHz, CDCl₃) δ 7.39 (s, 2H), 7.25-7.18 (m, 3H), 6.58(d, J=16.0 Hz, 1H), 6.30 (dd, J=16.0, 8.4 Hz, 1H), 5.91-5.70 (br, 2H),4.05 (m, 1H), 3.05-2.80 (m, 6H), 2.70 (m, 1H), 1.81 (m, 1H); ESIMS m/z492.17 ([M+H]⁺); IR (thin film) 3211, 1569, 1113, 806 cm⁻¹.

Compounds BC2-BC3 in Table 1 were made in accordance with the proceduresdisclosed in Example 26.

Example 27 Preparation of(E)-3,3,3-Trifluoro-N-(5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1H-inden-1-yl)propanamide(BC4)

To a stirred solution of(E)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1H-inden-1-amine(0.1 g, 0.23 mmol) in CH₂Cl₂ (10 mL) were added trifluoropropionic acid(0.044 g, 0.34 mmol), EDC.HCl (0.038 g, 0.35 mmol), HOBt.H₂O (0.07 g,0.46 mmol) and DIPEA (0.074 g, 0.57 mmol), and the reaction mixture wasstirred for 16 h at 25° C. The reaction mixture was diluted with CH₂Cl₂and washed with H₂O. The combined organic layer was washed with brine,dried over anhydrous Na₂SO₄, and concentrated under reduced pressure.The crude material was purified by flash column chromatography (SiO₂,15% EtOAc in petroleum ether) to afford the title compound as a liquid(65 mg, 65%): ¹H NMR (400 MHz, CDCl₃) δ 7.39 (s, 2H), 7.25-7.20 (m, 3H),6.34 (d, J=16.0 Hz, 1H), 6.30 (dd, J=16.0, 8.0 Hz, 1H), 5.81 (br, 1H),5.48 (m, 1H), 4.10 (m, 1H), 3.10 (m, 2H), 2.86-3.07 (m, 2H), 2.86 (m,1H), 1.81 (m, 1H); ESIMS m/z 529.02 ([M+H]⁺); IR (thin film) 3283, 1652,1241, 811 cm⁻¹.

Compounds BC5-BC9, BC11 in Table 1 were made in accordance with theprocedures disclosed in Example 27.

Example 28 Preparation of tert-Butyl 5-vinylindoline-1-carboxylate(BI10)

Step 1. 5-Bromo-indoline (BI11)

To 5-Bromo-1H-indole (2.5 g, 12.82 mmol) in acetic acid (10.0 mL),NaCNBH₃ (2.38 g, 38.46 mmol) was added portion wise at 10° C. over theperiod of 20 min. After that the reaction mixture was stirred at ambienttemperature for 3 h. The reaction mixture was diluted with water andextracted with diethyl ether. The organic layer was washed withsaturated NaHCO₃, water and brine solution. The combined ether layer wasdried over anhydrous Na₂SO₄ and concentrated under reduced pressure toafford title compound as a pale yellow semi-solid (1.8 g, 71%).

Step 2. tert-Butyl-5-bromoindoline-1-carboxylate (BI12)

To a stirred solution of 5-bromo-indoline (3.0 g, 15 mmol) inacetonitrile (100 ml), was added DMAP (0.185 g, 1.522 mmol) anddi-tert-butyl dicarbonate (3.98 g, 18.3 mmol) and the reaction wasstirred at ambient temperature for 16 h. The reaction mixture wasconcentrated on reduced pressure to obtain a residue which was dilutedwith diethyl ether and washed with water and brine solution (2×). Thecombined ether layer was dried over anhydrous Na₂SO₄ and concentratedunder reduced pressure to afford the crude product as an off-whitesolid, which was used in the next step without further purification (3.0g).

Step 3. tert-Butyl-5-vinylindoline-1-carboxylate (BI10)

A stirred solution of tert-butyl-5-bromoindoline-1-carboxylate (2.0 g,6.73 mmol), potassium vinyl trifluoroborate (2.6 g, 20.20 mmol) andK₂CO₃ (2.78 g, 20.2 mmol) in DMSO (50.0 mL) was degassed with argon for20 min at ambient temperature. PdCl₂(dppf) (0.49 g, 0.67 mmol) was addedat ambient temperature, then the reaction mixture was heated to 100° C.for 3 h. The reaction mixture was cooled to ambient temperature andfiltered through a celite bed under vacuum and washed with diethylether. The reaction mixture was extracted with diethyl ether. Thecombined diethyl ether layer was dried over Na₂SO₄ and concentratedunder reduced pressure to afford crude product. The crude compound waspurified by column chromatography (SiO₂, 100-200 mesh; eluting with 2%ethyl acetate/petroleum ether) to afford the title compound as anoff-white solid (1.2 g, 73%): Mp 85.5-88.6° C.; ¹H NMR (400 MHz, CDCl₃)δ 7.23 (m, 3H), 6.69 (dd, J=17.4, 10.8 Hz, 1H), 5.64 (d, J=10.5 Hz, 1H),5.13 (d, J=10.5 Hz, 1H), 4.00 (t, J=9.0 Hz, 2H), 3.10 (t, J=9.0 Hz, 2H),1.55 (bs, 9H).

Example 29 Preparation of (E)-tert-Butyl5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)indoline-1-carboxylate(BI13)

To a stirred solution of tert-butyl-5-vinylindoline-1-carboxylate (1.28g, 5.23 mmol) in 1,2-dichlorobenzene (10.0 mL), was added5-(1-bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-fluorobenzene (3.4 g,10mmol), CuCl (103 mg, 1.05 mmol) and 2,2-bipyridyl (0.326 g, 2.092 mmol)and the resultant reaction mixture was degassed with argon for 30 minand heated to 150° C. for 1 h. The reaction mixture was cooled toambient temperature and filtered and the filtrate was concentrated underreduced pressure. The crude compound was purified by columnchromatography (SiO₂, 100-200 mesh; 2% ethyl acetate/petroleum ether) toafford the title compound as a pale yellow gummy solid (0.3 g, 61%): ¹HNMR (400 MHz, CDCl₃) δ 7.34 (d, J=6.0 Hz, 2H), 7.22 (s, 2H), 7.16 (d,J=8.4 Hz, 1H), 6.52 (d, J=16.0 Hz, 1H), 6.21 (dd, J=16.0, 7.6 Hz, 1H),4.07 (m, 3H), 3.10 (t, J=8.4 Hz, 2H), 1.55 (s, 9H); ESIMS m/z 433.79([M−H]⁻); IR (thin film) 1168, 858 cm⁻¹.

Example 30 Preparation of(E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)indolin-1-amine(BI14)

Step 1.(E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)indoline(BI15)

To a stirred solution of(E)-tert-butyl-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)indoline-1-carboxylate(0.2 g, 0.4 mmol) in CH₂Cl₂ (10.0 mL) was added TFA (0.6 mL) and thereaction was stirred at ambient temperature for 2 h. The reactionmixture was diluted with CH₂Cl₂, washed with saturated aq NaHCO₃, waterand brine solution. The separated CH₂Cl₂ layer was dried over anhydrousNa₂SO₄ and concentrated under reduced pressure to afford the crudeproduct as a light brown gummy material which was used in the next stepwithout further purification (0.12 g): ¹H NMR (400 MHz, CDCl₃) δ 7.33(d, J=6.4 Hz, 2H), 7.21 (s, 1H), 7.02 (d, J=8.0 Hz, 1H), 6.57 (d, J=8.4Hz, 1H), 6.49 (d, J=15.6 Hz, 1H), 6.21 (dd, J=15.6, 8.4 Hz, 1H), 4.07(m, 1H), 3.61 (t, J=8.4 Hz, 2H), 3.05 (t, J=8.4 Hz, 2H); ESIMS m/z389.89 ([M+H]⁺); IR (thin film) 3385, 1112, 816 cm⁻¹.

Step 2.5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1-nitrosoindoline(BI16)

To(E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)indoline(0.2 g, 0.5 mmol) in concentrated HCl (5.0 ml) at 5° C., was addedslowly NaNO₂ in water and the reaction was allowed to stir at ambienttemperature for 2 h. The reaction mixture was diluted with CH₂Cl₂, andthe CH₂Cl₂ layer washed with water and brine solution. The separatedCH₂Cl₂ layer was dried over anhydrous Na₂SO₄ and concentrated underreduced pressure to afford the crude product as a pale yellow solid thatwas used in the next step without further purification (0.2 g): ¹H NMR(400 MHz, CDCl₃) δ 7.33 (d, J=8.4 Hz, 1H), 7.39 (m, 4H), 6.61 (d, J=16.0Hz, 1H), 6.35 (dd, J=16.0, 8.4 Hz, 1H), 4.07 (m, 3H), 3.23 (t, J=8.4 Hz,2H); ESIMS m/z 418.82 ([M+H]⁺); IR (thin film) 1488, 1112, 860 cm⁻¹.

Step 3.(E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)indolin-1-amine(BI14)

To(E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1-nitrosoindoline(0.1 g, 0.2 mmol) in MeOH(10.0 mL) was added zinc powder (77.5 mg) andNH₄Cl (36.9 mg, 0.69 mmol) in water (2.0 mL). The reaction mixture wasstirred at ambient temperature for 3 h. The reaction mixture was dilutedwith CH₂Cl₂ and the CH₂Cl₂ layer was washed with water and brinesolution. The separated CH₂Cl₂ layer was dried over anhydrous Na₂SO₄ andconcentrated under reduced pressure to afford the crude compound, whichwas purified by column chromatography (SiO₂, 100-200 mesh; eluting with2% ethyl acetate/petroleum ether) to afford the title compound as alight brown gummy material (0.08 g): ESIMS m/z 404.86 ([M+H]⁺).

Example 31 Preparation of(E)-N-(5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)indolin-1-yl)-3,3,3-trifluoropropanamide(BC12)

To a stirred solution of(E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)indoline-1-amine(0.1 g, 0.247 mmol) in CH₂Cl₂ (10.0 ml) was added3,3,3-trifluoropropanoic acid (0.038 g, 0.297 mmol), PyBOP (0.192 g,0.370 mmol) and DIPEA (0.047 g, 0.370 mmol) and the reaction was stirredat ambient temperature for 18 h. The reaction mixture was diluted withCH₂Cl₂, and the separated CH₂Cl₂ layer dried over anhydrous Na₂SO₄ andconcentrated under reduced pressure to afford the crude compound. Thecrude compound was purified by column chromatography (SiO₂, 100-200mesh; 20-25% ethyl acetate/petroleum ether) to afford the title compoundas a light brown gummy material (0.12 g, 33%): ¹H NMR (400 MHz, CDCl₃) δ7.32, (d, J=6.0 Hz, 2H) 7.28 (m, 1H), 7.20 (d, J=8.0, 1H), 7.14 (d,J=8.8, 1H), 6.70 (d, J=8.0 Hz, 1H), 6.60 (m, 2H), 4.15 (m, 1H), 3.85 (m,1H), 3.65 (m, 1H), 3.46 (m, 2H), 3.19 (m, 2H); ESIMS m/z 514.86([M+H]⁺); IR (thin film) 3428, 1112, 857 cm⁻¹.

Example 32 Preparation of tert-Butyl-5-vinyl-1H-indole-1-carboxylate(BI17)

Step 1. 5-Vinyl-1H-indole (BI18)

A mixture of 5-bromo-1H-indole (2.5 g, 12.82 mmol), potassiumvinyltrifluoroborate (2.57 g, 19.2 mmol), Cs₂CO₃ (12.53 g, 38.46 mmol)and triphenylphosphine (201 mg, 0.769 mmol) in THF/water (9:1, 75 ml)was degassed with argon for 20 min, then charged with PdCl₂ (45.3 mg,0.256 mmol). The reaction mixture was heated to reflux for 16 h, thencooled to ambient temperature, filtered through celite bed and washedwith ethyl acetate. The filtrate was again extracted with ethyl acetate,and the combined organic layer washed with water and brine, dried overNa₂SO₄ and concentrated under reduced pressure to afford the crudecompound. The crude compound was purified by column chromatography(SiO₂, 100-200 mesh; 2% ethyl acetate/petroleum ether) to afford thetitle compound as a light brown gummy material (1.5 g, 83%): ¹H NMR (400MHz, CDCl₃) δ 8.20 (br, 1H), 7.68 (s, 1H), 7.45 (s, 2H), 7.21 (m, 1H),6.90 (dd, J=16.0, 10.8 Hz, 1H), 6.55 (m, 1H), 5.75 (d, J=10.5 Hz, 1H),5.21 (d, J=10.5 Hz, 1H); ESIMS m/z 142.05 ([M−H]⁻).

Step 2. tert-Butyl-5-vinyl-1H-indole-1-carboxylate (BI17)

To a stirred solution of 5-vinyl-1H-indole (0.7 g, 4.89 mmol) inacetonitrile (20 ml) was added DMAP (59.65 mg, 0.489 mmol) anddi-tert-butyl dicarbonate (1.38 g, 6.36 mmol), and the reaction wasstirred at ambient temperature for 3 h. The reaction mixture wasconcentrated under reduced pressure to obtain a residue which wasdiluted with CH₂Cl₂ and washed with water and brine solution. Thecombined CH₂Cl₂ layer was dried over anhydrous Na₂SO₄ and concentratedunder reduced pressure to afford the crude compound. The crude compoundwas purified by column chromatography (SiO₂, 100-200 mesh; 2% ethylacetate/petroleum ether) to afford the title compound as an off-whitesemi-solid (0.7 g, 59%): ¹H NMR (400 MHz, CDCl₃) δ 8.15 (d, J=8.0 Hz,1H), 7.60 (s, 2H), 7.30 (d, J=8.4 Hz, 1H), 7.21 (m, 1H), 6.90 (dd,J=16.0, 10.8 Hz, 1H), 6.59 (s, 1H), 5.75 (d, J=10.5 Hz, 1H), 5.21 (d,J=10.5 Hz, 1H), 1.65 (s, 9H); ESIMS m/z 242.10 ([M−H]⁻); IR (thin film)1630 cm⁻¹.

Example 33 Preparation of (E)-tert-Butyl5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1H-indole-1-carboxylate(BI19)

To a stirred solution of tert-butyl 5-vinyl-1H-indole-1-carboxylate(0.65 g, 2.67 mmol), in 1,2-dichlorobenzene (10.0 mL) was added5-(1-bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-fluorobenzene (1.74 g,5.37 mmol), CuCl (53 mg, 0.537 mmol) and 2,2-bipyridyl (167 mg, 1.07mmol). The resultant reaction mixture was degassed with argon for 30 minand heated to 150° C. for 2 h. The reaction mixture was cooled toambient temperature and filtered, and the filtrate concentrated underreduced pressure. The crude compound was purified by columnchromatography (SiO₂, 100-200 mesh; 2% ethyl acetate/petroleum ether) toafford the title compound as a light brown gummy material (0.25 g, 10%):¹H NMR (400 MHz, CDCl₃) δ 8.20 (d, J=8.0 Hz, 1H), 7.60 (m, 2H), 7.39 (m,3H), 6.69 (d, J=16.0 Hz, 1H), 6.55 (d, J=10.5 Hz, 1H), 6.36 (dd, J=16.0,8.0 Hz, 1H), 4.10 (m, 1H), 1.65 (s, 9H); ESIMS m/z 485.91 ([M−H]⁻); IR(thin film) 1165, 854 cm⁻¹.

Example 34 Preparation of(E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1H-indole(BI20)

To a stirred solution of (E)-tert-butyl5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1H-indole-1-carboxylate(0.2 g, 0.40 mmol) in CH₂Cl₂ (10.0 mL) was added TFA (70 mg, 0.61 mmol)and the reaction was stirred at ambient temperature for 2 h. Thereaction mixture was diluted with CH₂Cl₂ and washed with saturatedNaHCO₃ solution, water and brine solution. The separated CH₂Cl₂ layerwas dried over anhydrous Na₂SO₄ and concentrated under reduced pressureto afford the title compound as a light brown solid (0.2 g, 97%): mp132.9-138.8° C.; ¹H NMR (400 MHz, CDCl₃) δ 11.19 (br, 1H), 8.20 (d,J=8.0 Hz, 1H), 7.60 (m, 2H), 7.39 (m, 3H), 6.69 (d, J=16.0 Hz, 1H), 6.55(d, J=10.5 Hz, 1H), 6.36 (dd, J=16.0, 8.0 Hz, 1H), 4.82 (m, 1H); ESIMSm/z 387.98 ([M+H]⁺).

Example 35 Preparation of 4-Nitrophenyl2-((tert-butoxycarbonyl)amino)acetate (BI21)

To a stirred solution of 4-nitrophenol (1.0 g, 7.19 mmol) in CH₂Cl₂(20.0 mL) was added N-Boc glycine (1.38 g, 7.91 mmol) and EDC HCl (2.05g, 10.785 mmol) and the reaction was stirred at ambient temperature for24 h. The reaction mixture was diluted with CH₂Cl₂ and washed with waterand saturated brine solution. The separated CH₂Cl₂ layer was dried overanhydrous Na₂SO₄ and concentrated under reduced pressure to afford thetitle compound as a light brown gummy material that was used in the nextstep without further purification (1.1 g): ¹H NMR (400 MHz, CDCl₃) δ8.29 (d, J=9.2 Hz, 2H), 7.33 (d, J=8.8 Hz, 2H), 5.07 (br, 1H), 4.20 (s,2H), 1.47 (s, 9H); ESIMS m/z 296.27 ([M+H]⁺).

Example 36 Preparation of (E)-tert-Butyl(2-(5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1H-indol-1-yl)-2-oxoethyl)carbamate(BI22)

To a stirred solution of(E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1H-indole(0.1 g, 0.258 mmol) in acetonitrile (5.0 mL) was added 4-nitrophenyl2-(tert-butoxycarbonylamino) acetate (0.114 g, 0.387 mmol), potassiumfluoride (0.03 g, 0.516 mmol), 18-crown-6-ether (0.075 g, 0.283 mmol)and DIPEA (0.0332 g, 0.258 mmol) and the reaction was stirred at ambienttemperature for 16 h. The reaction mixture was concentrated to obtain aresidue which was diluted with CH₂Cl₂ and washed with water and brinesolution. The separated CH₂Cl₂ layer was dried over anhydrous Na₂SO₄ andconcentrated under reduced pressure to afford the crude title compoundas a light brown gummy material which was used in the next step withoutfurther purification (0.1 g): ESIMS m/z 545.23 ([M+H]⁺).

Example 37 Preparation of(E)-N-(2-(5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1H-indol-1-yl)-2-oxoethyl)-3,3,3-trifluoropropanamide(BC13)

Step 1.(E)-2-Amino-1-(5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1H-indol-1-yl)ethanone(BI23)

To a stirred solution of (E)-tert-butyl2-(5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1H-indol-1-yl)-2-oxoethylcarbamate(0.05 g, 0.09 mmol) in CH₂Cl₂ (5.0 mL) was added TFA (0.01 mL) and thereaction was stirred at ambient temperature for 16 h. The reactionmixture was diluted with CH₂Cl₂ and washed with saturated NaHCO₃solution, water and brine solution. The separated CH₂Cl₂ layer was driedover anhydrous Na₂SO₄ and concentrated under reduced pressure to affordthe crude title compound which was used in the next step without furtherpurification (50 mg).

Step 2.(E)-N-(2-(5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1H-indol-1-yl)-2-oxoethyl)-3,3,3-trifluoropropanamide(BC13)

To a stirred solution of(E)-2-amino-1-(5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1H-indol-1-yl)ethanone (0.04 g, 0.09 mmol) in CH₂Cl₂ (5.0 ml) was added3,3,3-trifluoropropanoic acid (17.5 mg, 0.136 mmol), PyBOP (70 mg, 0.135mmol) and DIPEA (29 mg, 0.225 mmol) and the reaction was stirred atambient temperature for 16 h. The reaction mixture was diluted withCH₂Cl₂, and the CH₂Cl₂ layer was washed with water and saturated brinesolution. The separated CH₂Cl₂ layer was dried over anhydrous Na₂SO₄ andconcentrated under reduced pressure to afford the crude compound, whichwas purified by column chromatography (SiO₂, 100-200 mesh; 10% ethylacetate/petroleum ether) to afford the title compound as an off-whitesolid (30 mg, 60%): mp 121-126° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.33 (br,1H), 7.59 (s, 1H), 7.45 (m, 4H), 6.72 (d, J=3.6 Hz, 3H), 6.39 (m, 1H),4.71 (t, J=7.2 Hz, 2H), 4.15 (m, 1H), 3.51 (m, 1H), 3.28 (m, 1H); ESIMSm/z 553.06 ([M−H]⁻).

Example 38 Preparation of Ethyl2-(1-oxo-6-vinylphthalazin-2(1H)-yl)acetate (BI24)

Step 1. 5-Bromo-3-hydroxyisoindoline-1-one (BI25)

A mixture of Zn powder (1.73 g, 26.154 mmol), copper (II) sulfatepentahydrate (0.02 g, 0.08 mmol) and 2M aq NaOH (27 mL) were cooled to0° C. 5-Bromoisoindoline-1,3-dione (5 g, 22 mmol) was added at the sametemperature over the period of 30 min. The reaction mixture was stirredat 0° C. for 30 min and 3 h at ambient temperature. The reaction mixturewas filtered and the filtrate was neutralized with concentrated HCl. Thereaction mixture was diluted with ethanol and extracted with ethylacetate. The combined ethyl acetate layer was dried over Na₂SO₄ andconcentrated under reduced pressure to afford the crude title compoundas a brown solid, which was used in the next step without furtherpurification (1.3 g): mp 258-261° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 9.03(br, 1H), 7.81 (m, 2H), 7.69 (m, 1H), 6.44 (m, 1H), 5.88 (d, J=9.3 Hz,1H); ESIMS m/z 225.83 ([M−H]⁻); IR (thin film) 1684, 3246, 606 cm⁻¹.

Step 2. 6-Bromophthalazine-1(2H)-one (BI26)

To a stirred solution of 5-bromo-3-hydroxyisoindoline-1-one (1.0 g, 4.40mmol) in water, was added hydrazine hydrate (0.45 g, 8.80 mmol) andheated to 95° C. for 5 h. The reaction mixture was cooled to ambienttemperature, filtered and washed with diethyl ether and pentane (1:1) toafford the title compound as a white solid that was used in the nextstep without further purification (0.5 g): ESIMS m/z 225.15 ([M+H]⁺).

Step 3. 6-Vinylphthalazine-1(2H)-one (BI27)

A solution of 6-bromophthalazine-1(2H)-one (0.25 g, 1.11 mmol),potassium vinyl trifluoroborate (0.446 g, 3.33 mmol) and K₂CO₃ (0.46 g,3.33 mmol) in DMSO (2 mL) was degassed with argon for 20 min at ambienttemperature. PdCl₂(dppf) (0.04 g, 0.055 mmol) was added at ambienttemperature, and the reaction mixture was heated to 80° C. for 2 h. Thereaction mixture was cooled to ambient temperature and filtered throughcelite bed under vacuum and washed with ethyl acetate. The reactionmixture was extracted with ethyl acetate and the combined ethyl acetatelayer dried over Na₂SO₄ and concentrated under reduced pressure toafford the crude product. The crude compound was purified by columnchromatography (SiO₂, 100-200 mesh; 50% ethyl acetate/petroleum ether)to afford the title compound as a brown solid (0.12 g, 63%): ¹H NMR (400MHz, DMSO-d₆) δ 13.61 (br, 1H), 8.33 (m, 1H), 8.19 (m, 1H), 8.01 (m,2H), 6.97 (m, 1H), 6.15 (m, 1H), 5.56 (d, J=10.8 Hz, 1H); ESIMS m/z172.93 ([M+H]±); IR (thin film) 1748, 1655, 3241 cm⁻¹.

Step 4. Ethyl-2-(1-oxo-6-vinylphthalazine-2(1H)-yl acetate (BI24)

To a stirred solution of 6-vinylphthalazine-1(2H)-one (0.5 g, 2.90 mmol)in DMF (5.0 mL) was added Cs₂CO₃ (0.94 g, 2.90 mmol) and the reactionwas stirred for 10 min Ethyl bromoacetate (0.48 g, 2.90 mmol) was addedto the reaction mixture at ambient temperature and the reaction wasstirred for 8 h at ambient temperature. The reaction mixture was dilutedand extracted with ethyl acetate, and the ethyl acetate layer was washedwith water and brine solution (2×). The separated ethyl acetate layerwas dried over anhydrous Na₂SO₄ and concentrated under reduced pressureto afford crude product. The crude compound was purified by columnchromatography (SiO₂, 100-200 mesh; 25% ethyl acetate/petroleum ether)to afford the title compound as a brown solid (0.34 g, 45%): ¹H NMR (400MHz, DMSO-d₆) δ 8.45 (m, 1H), 8.24 (m, 1H), 8.04 (m, 2H), 7.01 (m, 1H),6.17 (d, J=2.1 Hz, 1H), 5.56 (d, J=10.8 Hz, 1H), 4.92 (s, 2H), 4.19 (m,2H), 1.23 (m, 3H). ESIMS m/z 259.10 ([M+H]±); IR (thin film) 1750, 1660cm⁻¹.

Example 39 Preparation of (E)-Ethyl2-(6-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1-oxophthalazin-2(1H)-yl)acetate(BI28)

To a stirred solution of ethyl-2-(1-oxo-6-vinylphthalazine-2(1H)-ylacetate (0.07 g, 0.27 mmol) in 1,2-dichlorobenzene (1.0 mL) was added5-(1-bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2fluorobenzene (0.17 g,0.54 mmol), CuCl (0.005 g, 0.05 mmol) and 2,2-bipyridyl (0.016 g, 0.10mmol) and the resultant reaction mixture was degassed with argon for 30min and heated to 180° C. for 12 h. The reaction mixture was cooled toambient temperature and filtered and the filtrated was concentratedunder reduced pressure. The crude compound was purified by columnchromatography (SiO₂, 100-200 mesh; 10-15% ethyl acetate/petroleumether) to afford the title compound as a brown solid (40 mg, 29%): ¹HNMR (400 MHz, DMSO-d₆) δ 8.40 (d, J=8.4 Hz, 1H), 7.84 (d, J=1.5 Hz, 1H),7.65 (s, 1H), 7.37 (d, J=6.3 Hz, 2H), 6.76 (d, J=16.0 Hz, 1H), 6.59 (dd,J=16.0, 8.0 Hz, 1H), 4.96 (s, 2H), 4.29 (m, 3H), 1.31 (t, J=7.2 Hz, 3H);ESIMS m/z 503.0 ([M+H]⁺); IR (thin film) 1660, 1114, 817 cm⁻¹.

Example 40 Preparation of(E)-2-(6-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1-oxophthalazin-2(1H)-yl)aceticacid (BI29)

A solution of(E)-ethyl-2-(6-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1-oxophthalazin-2(1H)-yl)acetate (0.04 g, 0.07 mmol) in HCl (0.5 mL) and acetic acid (0.5 mL) washeated to 100° C. for 3 h. The solvent was removed under reducedpressure and the residue diluted with water. The aqueous layer wasextracted with ethyl acetate and the separated ethyl acetate layer driedover anhydrous Na₂SO₄ and concentrated under reduced pressure to affordthe crude compound. The crude compound was triturated with diethylether-pentane mixture to afford the title compound as a brown solid(0.03 g): ¹H NMR (400 MHz, DMSO-d₆) δ 13.0 (br s, 1H), 8.43 (m, 1H),8.23 (d, J=8.1 Hz, 1H), 8.14 (m, 2H), 7.91 (m, 2H), 7.16 (dd, J=16.0,8.0 Hz, 1H), 6.99 (d, J=16.0 Hz, 1H), 4.96 (m, 3H); ESIMS m/z 473.0([M−H]⁻); IR (thin film) 1629, 1168, 817 cm⁻¹.

Example 41 Preparation of(E)-2-(6-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1-oxophthalazin-2(1H)-yl)-N-(2,2,2-trifluoroethyl)acetamide(BC14)

To a stirred solution of(E)-2-(6-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1-oxophthalazin-2(1H)-yl)aceticacid (0.15 g, 0.31 mmol) in CH₂Cl₂ (20.0 ml) was added2,2,2,-trifluoroethanamine (0.03 g, 0.31 mmol), PyBOP (0.17 g, 0.34mmol) and DIPEA (0.15 ml, 0.93 mmol) at ambient temperature, and thereaction was stirred for 18 h. The reaction mixture was diluted withCH₂Cl₂ and washed with 3N HCl (2×20 mL), NaHCO₃ (2×20 mL) and brinesolution (2×).The separated CH₂Cl₂ layer was dried over anhydrous Na₂SO₄and concentrated under reduced pressure to afford the crude compound.The crude compound was purified by column chromatography (SiO₂, 100-200mesh; 20-25% ethyl acetate/petroleum ether) to afford the title compoundas a brown solid (0.11 g): mp 172-175° C.; ¹H NMR (400 MHz, CDCl₃) δ8.83 (t, J=6.6 Hz, 1H), 8.42 (t, J=14.7 Hz, 1H), 8.22 (d, J=8.1 Hz, 1H),8.13 (t, J=6.3 Hz, 1H), 7.98-7.86 (m, 2H), 7.16-7.07 (m, 1H), 7.01-6.93(m, 1H), 4.96-4.81 (m, 3H), 4.00-3.88 (m, 2H); ESIMS m/z 554.0 ([M−H]⁻).

Example 42 Preparation of 2-(4-Vinylbenzyl)isoindoline-1,3-dione (CI1)

To a stirred solution of 1-(chloromethyl)-4-vinylbenzene (10 g, 66 mmol)in DMF (100 mL) was added potassium phthalimide (13.3 g, 72.1 mmol), andthe resultant reaction mixture was heated at 70° C. for 16 h. Thereaction mixture was diluted with H₂O and extracted with CHCl₃. Thecombined CHCl₃ layer was washed with brine, dried over Na₂SO₄ andconcentrated under reduced pressure. Recrystallization from MeOHafforded the title compound as an off-white solid (8 g, 46%): ¹H NMR(400 MHz, CDCl₃) δ 7.83 (m, 2H), 7.71 (m, 2H), 7.39 (m, 4H), 6.65 (dd,J=17.6, 10.8 Hz, 1H), 5.72 (d, J=17.6 Hz, 1H), 5.21 (d, J=10.8 Hz, 1H),4.82 (s, 2H); GCMS m/z 263.2 ([M]⁺); IR (thin film) 3420, 1133, 718cm⁻¹.

Example 43 Preparation of(E)-2-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)isoindoline-1,3-dione(CI2)

Using the procedure of Example 10 with2-(4-vinylbenzyl)isoindoline-1,3-dione and1-(1-bromoethyl)-3,5-dichlorobenzene as the starting materials, thetitle compound was isolated as an off-white solid (0.3 g, 40-50%): mp142-145° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.86 (m, 2H), 7.74 (m, 2H), 7.42(m, 2H), 7.36 (m, 3H), 7.27 (m, 2H), 6.58 (d, J=16.0 Hz, 1H), 6.32 (dd,J=16.0, 8.0 Hz, 1H), 4.82 (s, 2H), 4.05 (m, 1H); ESIMS m/z 488.17([M−H]⁻).

The following compound was made in accordance with the proceduresdisclosed in Example 43.

(E)-2-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)isoindoline-1,3-dione(CI3)

The title compound was isolated as an off white solid (0.3 g, 56%): mp145-146° C.;

¹H NMR (400 MHz, CDCl₃) δ 7.86 (m, 2H), 7.74 (m, 2H), 7.42-7.31 (m, 6H),6.58 (d, J=16.0 Hz, 1H), 6.53 (dd, J=16.0, 8.0 Hz, 1H), 4.82 (s, 2H),4.05 (m, 1H); ESIMS m/z 522.2 ([M−H]⁻); IR (thin film) 1716, 1110, 712cm⁻¹.

Prophetically, compounds CI4-CI5 (Table 1) could be made in accordancewith the procedures disclosed in Example 43.

Example 44 Preparation of(E)-(4-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine(CI6)

To a stirred solution of(E)-2-(4-(3-(3,5-dichlorophenyl)but-1-en-1-yl)benzyl)-isoindoline-1,3-dione(1.2 g, 2.45 mmol) in EtOH was added hydrazine hydrate (0.61 g, 12mmol), and the resultant reaction mixture was heated at 90° C. for 1 h.The reaction mixture was filtered, and the filtrate was concentrated.The residue was dissolved in CH₂Cl₂, washed with brine, dried overNa₂SO₄, and concentrated under reduced pressure to afford the crudetitle compound as a gummy liquid (0.9 g) which was used without furtherpurification.

The following compounds were made in accordance with the proceduresdisclosed in Example 44.

(E)-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-phenyl)methanamine(CI7)

The title compound was isolated and used without further purification.

Prophetically, compounds CI8-CI9 (Table 1) could be made in accordancewith the procedures disclosed in Example 44.

Example 45 Preparation of 4-(Bromomethyl)-3-chlorobenzonitrile (CI10)

To a stirred solution of 3-chloro-4-methylbenzonitrile (5 g, 25.4 mmol)in carbon tetrachloride (CCl₄; 50 mL) under an argon atmosphere wasadded NBS (5.16 g, 29 mmol), and the mixture was degassed for 30 min. Tothis was added azobisisobutyronitrile (AIBN; 0.3 g, 1.8 mmol), and theresultant reaction mixture was heated at reflux for 4 h. The reactionmixture was cooled to ambient temperature, washed with H₂O, andextracted with CH₂Cl₂. The combined CH₂Cl₂ layer was washed with brine,dried over Na₂SO₄, and concentrated under reduced pressure. The crudecompound was purified by flash column chromatography (SiO₂, 100-200mesh; 5% EtOAc in n-Hexane) to afford the title compound as a whitesolid (4.8 g, 68%): mp 87-88° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.71 (s,1H), 7.59 (s, 2H), 4.60 (s, 2H); ESIMS m/z 229.77 ([M+H]⁺); IR (thinfilm) 2235, 752, 621 cm⁻¹.

The following compounds were made in accordance with the proceduresdisclosed in Example 45.

4-(Bromomethyl)-3-(trifluoromethyl)benzonitrile (CI11)

The title compound was isolated as an off-white gummy material (5 g,66%): ¹H NMR (400 MHz, CDCl₃) δ 7.96 (s, 1H), 7.86 (d, J=8.0 Hz, 1H),7.76 (d, J=8.0 Hz, 1H), 4.62 (s, 2H); ESIMS m/z 262.11 ([M−H]⁻); IR(thin film) 2236, 1132, 617 cm⁻¹.

3-Bromo-4-(bromomethyl)benzonitrile (CI12)

The title compound was isolated as an off-white solid (5 g, 67%): mp82-83° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.90 (s, 1H), 7.61 (m, 2H), 4.62(s, 2H); EIMS m/z 272.90; IR (thin film) 2229, 618 cm⁻¹.

4-(Bromomethyl)-3-fluorobenzonitrile (CI13)

The title compound was isolated as an off-white solid (2 g, 60%): mp79-81° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.54 (t, J=8.0 Hz, 1H), 7.48 (dd,J=8.0 Hz, 8.0, 1H), 7.38 (dd, J=5 Hz, 1H), 4.5 (s, 2H); EIMS m/z 215.

Example 46 Preparation of 4-(Bromomethyl)-3-chlorobenzaldehyde (CI14)

To a stirred solution of 4-(bromomethyl)-3-chlorobenzonitrile (4.8 g, 17mmol) in toluene (50 mL) at 0° C. was added dropwise diisobutylaluminumhydride (DIBAL-H, 1.0 M solution in toluene; 23.9 mL), and the reactionmixture was stirred at 0° C. for 1 h. 10 M HCl in H₂O (5 mL) was addeduntil the reaction mixture turned to a white slurry and then additional1 N HCl (20 mL) was added. The organic layer was collected and theaqueous layer was extracted with CHCl₃. The combined organic layer wasdried over Na₂SO₄ and concentrated under reduced pressure. The crudecompound was purified by flash column chromatography (SiO₂, 100-200mesh; 5% EtOAc in n-Hexane) to afford the title compound as a whitesolid (3.8 g, 80%): mp 64-66° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.00 (s,1H), 7.92 (s, 1H), 7.78 (d, J=8.0 Hz, 1H), 7.64 (d, J=8.0 Hz, 1H), 4.60(s, 2H); ESIMS m/z 232.78 ([M+H]⁺).

The following compounds were made in accordance with the proceduresdisclosed in Example 46.

4-(Bromomethyl)-3-(trifluoromethyl)benzaldehyde (CI15)

The title compound was isolated as a pale yellow low-melting solid (5 g,60%): ¹H NMR (400 MHz, CDCl₃) δ 10.09 (s, 1H), 8.19 (s, 1H), 8.09 (m,1H), 7.81 (m, 1H), 4.61 (s, 2H); ESIMS m/z 265.04 ([M−H]⁻); IR (thinfilm) 1709, 1126, 649 cm⁻¹.

3-Bromo-4-(bromomethyl)benzaldehyde (CI16)

The title compound was isolated as a pale yellow solid (5 g, 62%): mp94-95° C.; ¹H NMR (400 MHz, CDCl₃) δ 9.96 (s, 1H), 8.05 (s, 1H), 7.81(d, J=8.0 Hz, 1H), 7.62 (d, J=8.0 Hz, 1H), 4.60 (s, 2H); EIMS m/z275.90.

4-(Bromomethyl)-3-fluorobenzaldehyde (CI17)

The title compound was isolated as an off-white solid (5 g, 61%): mp43-45° C.; ¹H NMR (400 MHz, CDCl₃) δ 9.1 (s, 1H), 7.54 (t, J=8 Hz, 1H),7.48 (d, J=8 Hz, 1H), 7.38 (d, J=5 Hz, 1H), 4.5 (s, 2H); EIMS m/z 216.

Example 47 Preparation of3-Chloro-4-((1,3-dioxoisoindolin-2-yl)methyl)benzaldehyde (CI18)

To a stirred solution of 4-(bromomethyl)-3-chlorobenzaldehyde (3.8 g, 14mmol) in DMF (40 mL) was added potassium pthalimide (3.54 g, 19.14mmol), and the mixture was heated at 60° C. for 6 h. The reactionmixture was cooled to ambient temperature and diluted with H₂O (100 mL).The solid obtained was separated by filtration and dried under vacuum toafford the title compound as a white solid (2.8 g, 60%): mp 123-126° C.;¹H NMR (400 MHz, CDCl₃) δ 9.95 (s, 1H), 8.21 (s, 1H), 7.91 (m, 3H), 7.80(m, 2H), 7.20 (m, 1H), 5.05 (s, 2H); ESIMS m/z 298.03 ([M−H]⁻).

The following compounds were made in accordance with the proceduresdisclosed in Example 47.

4-((1,3-Dioxoisoindolin-2-yl)-3-(trifluoromethyl)benzaldehyde (CI19)

The title compound was isolated as an off white solid (1 g, 62%): mp142-143° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.05 (s, 1H), 8.15 (s, 1H), 7.91(m, 2H), 7.80 (m, 3H), 7.27 (m, 1H), 5.19 (s, 2H); ESIMS m/z 332.03([M−H]⁻).

3-Bromo-4-((1,3-dioxoisoindolin-2-yl)methyl)benzaldehyde (CI20)

The title compound was isolated as an off-white solid (0.5 g, 64%): mp159-161° C.;

¹H NMR (400 MHz, CDCl₃) δ 9.95 (s, 1H), 8.21 (s, 1H), 7.91 (m, 3H), 7.80(m, 2H), 7.20 (m, 1H), 5.05 (s, 2H); ESIMS m/z 314.00 ([M−CHO]⁻).

4-((1,3-Dioxoisoindolin-2-yl)-3-fluorobenzaldehyde (CI21)

The title compound was isolated as a white solid (2 g, 60%): mp 154-156°C.; ¹H NMR (400 MHz, CDCl₃) δ 9.95 (s, 1H), 7.9 (m, 2H), 7.75 (m, 2H),7.6 (m, 2H), 7.5 (t, J=7.6 Hz, 1H), 5.05 (s, 2H); EIMS m/z 283.1.

Example 48 Preparation of2-(2-Chloro-4-vinylbenzyl)isoindoline-1,3-dione (CI22)

To a stirred solution of3-chloro-4-((1,3-dioxoisoindolin-2-yl)methyl)benzaldehyde (2.8 g, 8.2mmol) in 1,4-dioxane (30 mL) were added K₂CO₃ (1.68 g, 12.24 mmol) andmethyl triphenyl phosphonium bromide (4.37 g, 12.24 mmol) at ambienttemperature. Then the resultant reaction mixture was heated at 100° C.for 18 h. After the reaction was deemed complete by TLC, the reactionmixture was cooled to ambient temperature and filtered, and the obtainedfiltrate was concentrated under reduced pressure. The residue waspurified by flash chromatography (SiO₂, 100-200 mesh; 20% EtOAc inn-Hexane) to afford the title compound as a white solid (1.94 g, 70%):mp 141-143° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.85 (m, 2H), 7.70 (m, 2H),7.41 (m, 1H), 7.21 (m, 2H), 6.71 (dd, J=17.6, 10.8 Hz, 1H), 5.72 (d,J=17.6 Hz, 1H), 5.23 (d, J=10.8 Hz, 1H), 4.92 (s, 2H); ESIMS m/z 298.10([M−H]⁻).

The following compounds were made in accordance with the proceduresdisclosed in Example 48.

2-(2-(Trifluoromethyl)-4-vinylbenzyl)isoindoline-1,3-dione (CI23)

The title compound was isolated as a light brown solid (0.5 g, 60%): mp134-135° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.92 (m, 2H), 7.80 (m, 2H), 7.71(s, 1H), 7.46 (d, J=8.0 Hz, 1H), 7.16 (d, J=8.0 Hz, 1H), 6.65 (m, 1H),5.80 (d, J=17.8 Hz, 1H), 5.19 (d, J=10.8 Hz, 1H), 5.09 (s, 2H); ESIMSm/z 332.10 ([M+H]⁺).

2-(2-Bromo-4-vinylbenzyl)isoindoline-1,3-dione (CI24)

The title compound was isolated as an off white solid (0.5 g, 62%): mp126-128° C.;

¹H NMR (400 MHz, CDCl₃) δ 7.92 (m, 2H), 7.79 (m, 2H), 7.62 (s, 1H), 7.21(m, 1H), 7.16 (d, J=8.0 Hz, 1H), 6.62 (m, 1H), 5.72 (d, J=17.8 Hz, 1H),5.15 (d, J=10.8 Hz, 1H), 4.95 (s, 2H); EIMS m/z 341.10.

2-(2-Fluoro-4-vinylbenzyl)isoindoline-1,3-dione (CI25)

The title compound was isolated as a white solid (0.5 g, 61%): mp140-142° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.85 (m, 2H), 7.72 (m, 2H), 7.25(m, 1H), 7.11 (m, 2H), 6.63 (m, 1H), 5.80 (d, J=17.6 Hz, 1H), 5.28 (d,J=10.8 Hz, 1H), 4.92 (s, 2H); EIMS m/z 282.08.

Example 49 Preparation of(E)-2-(2-Chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)isoindoline-1,3-dione(CI26)

To a stirred solution of 2-(2-chloro-4-vinylbenzyl)isoindoline-1,3-dione(2.0 g, 6.51 mmol) in 1,2-dichlorobenzene (25 mL) were added1-(1-bromo-2,2,2-trifluoroethyl)-3,5-dichlorobenzene (3.48 g, 11.36mmol), CuCl (112 mg, 1.13 mmol) and 2,2-bipyridyl (0.35 g). Theresultant reaction mixture was degassed with argon for 30 min and thenwas stirred at 180° C. for 24 h. After the reaction was deemed completeby TLC, the reaction mixture was cooled to ambient temperature andfiltered, and the filtrate was concentrated under reduced pressure. Theresidue was purified by flash chromatography (SiO₂, 100-200 mesh; 25-30%EtOAc in n-hexane) to afford the title compound as solid (1.3 g, 50%):mp 141-143° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.92 (m, 2H), 7.79 (m, 2H),7.42 (m, 2H), 7.24 (m, 2H), 7.20 (m, 2H), 6.54 (d, J=16.0 Hz, 1H), 6.34(dd, J=16.0, 8.0 Hz, 1H), 5.00 (s, 2H), 4.10 (m, 1H); ESIMS m/z 524.07([M+H]⁺).

The following compounds were made in accordance with the proceduresdisclosed in Example 49.

(E)-2-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)isoindoline-1,3-dione(CI27)

The title compound was isolated as a pale white solid (0.2 g, 55%): mp128-129° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.92 (m, 2H), 7.79 (m, 2H), 7.42(m, 3H), 7.22 (m, 2H), 6.52 (d, J=16.0 Hz, 1H), 6.32 (dd, J=16.0, 8.0Hz, 1H), 5.00 (s, 2H), 4.05 (m, 1H); ESIMS m/z 557.99 ([M+H]⁺).

(E)-2-(2-Chloro-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)isoindoline-1,3-dione(CI28)

The title compound was isolated as an off white solid (0.2 g, 54%): mp177-180° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.90 (m, 2H), 7.77 (m, 2H), 7.42(s, 1H), 7.32 (d, J=8.0 Hz, 2H), 7.21 (m, 2H), 6.52 (d, J=16.0 Hz, 1H),6.32 (dd, J=16.0, 8.0 Hz, 1H), 5.00 (s, 2H), 4.05 (m, 1H); ESIMS m/z540.08 ([M−H]⁻); IR (thin film) 1716 cm⁻¹.

(E)-2-(2-Chloro-4-(3-(3,4-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)isoindoline-1,3-dione(CI29)

The title compound was isolated as an off-white solid (0.2 g, 59%): ¹HNMR (400 MHz, CDCl₃) δ 7.89 (m, 2H), 7.76 (m, 2H), 7.47 (m, 3H), 7.21(m, 3H), 6.50 (d, J=16.0 Hz, 1H), 6.32 (dd, J=16.0, 7.6 Hz, 1H), 4.97(s, 2H), 4.11 (m, 1H); ESIMS m/z 522.27 ([M−H]⁻); IR (thin film) 3064,1717, 1111, 715 cm⁻¹.

(E)-2-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)-benzyl)isoindoline-1,3-dione(CI30)

The title compound was isolated as an off-white solid (0.2 g, 54%): mp141-142° C.; ¹H NMR (400 MHz, CDCl₃) 7.94 (m, 2H), 7.80 (m, 2H), 7.69(s, 1H), 7.44 (m, 1H), 7.38 (m, 1H), 7.24 (m, 2H), 7.19 (m, 1H), 6.60(d, J=16.0 Hz, 1H), 6.39 (dd, J=16.0, 7.6 Hz, 1H), 5.10 (s, 2H), 4.11(m, 1H); ESIMS m/z 556.00 ([M−H]⁻).

(E)-2-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)-benzyl)isoindoline-1,3-dione(CI31)

The title compound was isolated as an off-white solid (0.2 g, 56%): mp130-132° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.94 (m, 2H), 7.80 (m, 2H), 7.69(s, 1H), 7.44 (m, 3H), 7.19 (m, 1H), 6.61 (d, J=16.0 Hz, 1H), 6.38 (dd,J=16.0, 7.6 Hz, 1H), 5.10 (s, 2H), 4.12 (m, 1H); ESIMS m/z 589.57([M−2H]⁻).

(E)-2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)-isoindoline-1,3-dione(CI32)

The title compound was isolated as a pale yellow solid (0.2 g, 55%): mp160-162° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.92 (m, 2H), 7.80 (m, 2H), 7.62(s, 1H), 7.39 (s, 2H), 7.24 (m, 1H), 7.16 (m, 1H), 6.52 (d, J=16.0 Hz,1H), 6.32 (dd, J=16.0, 8.0 Hz, 1H), 4.98 (s, 2H), 4.12 (m, 1H); ESIMSm/z 599.78 ([M−H]⁻).

(E)-2-(2-Fluoro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)-isoindoline-1,3-dione(CI33)

The title compound was isolated as an off-white solid (0.2 g, 55%): mp72-74° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.88 (m, 2H), 7.74 (m, 2H), 7.38(s, 2H), 7.34 (m, 1H), 7.18 (m, 2H), 6.54 (d, J=16.0 Hz, 1H), 6.32 (dd,J=16.0, 8.0 Hz, 1H), 4.91 (s, 2H), 4.08 (m, 1H); ESIMS m/z 539.89([M−H]⁻); IR (thin film) 1773 cm⁻¹.

Prophetically, compounds CI34-CI41 (Table 1) could be made in accordancewith the procedures disclosed in Example 49.

Example 50 Preparation of(E)-(2-Chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine(CI42)

To a stirred solution of(E)-2-(2-chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)isoindoline-1,3-dione(0.4 g, 0.76 mmol) in EtOH was added hydrazine hydrate (0.38 g, 7.6mmol), and the resultant reaction mixture was heated at 80° C. for 2 h.The reaction mixture was filtered, and the filtrate was concentrated.The residue was dissolved in CH₂Cl₂, washed with brine, dried overNa₂SO₄, and concentrated under reduced pressure to afford the titlecompound as a gummy liquid (0.3 g), which was carried on to the nextstep without further purification.

The following compounds were made in accordance with the proceduresdisclosed in Example 50.

(E)-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)-methanamine(CI43)

The product obtained in this reaction was carried on to the next stepwithout further purification.

(E)-(2-Chloro-4-(3-(3,4-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)-methanamine(CI44)

The product obtained in this reaction was carried on to the next stepwithout further purification: ¹H NMR (400 MHz, CDCl₃) δ 7.48 (d, J=8.4Hz, 2H), 7.39 (m, 2H), 7.23 (m, 2H), 6.52 (d, J=16.0 Hz, 1H), 6.38 (dd,J=16.0, 7.6 Hz, 1H), 4.12 (m, 1H), 3.90 (s, 2H); ESIMS m/z 391.90([M−H]⁻); IR (thin film) 3370, 3280, 1111, 817 cm⁻¹.

(E)-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)-phenyl)methanamine(CI45)

The title compound was isolated as a gummy material. The productobtained in this reaction was carried on to the next step withoutfurther purification.

(E)-(2-Bromo-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)-methanamine(CI46)

The title compound was isolated as a gummy material: The productobtained in this reaction was carried on to the next step withoutfurther purification.

(E)-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)-methanamine(CI47)

The title compound was isolated as a gummy material. The productobtained in this reaction was carried on to the next step withoutfurther purification.

(E)-(2-Fluoro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)-methanamine(CI48)

The title compound was isolated as a gummy material: ¹H NMR (400 MHz,CDCl₃) δ 7.40 (s, 2H), 7.33 (t, J=7.6 Hz, 1H), 7.13 (m, 2H), 6.56 (d,J=16.0 Hz, 1H), 6.33 (dd, J=16.0, 7.6 Hz, 1H), 4.08 (m, 1H), 3.90 (s,2H); ESIMS m/z 413.84 ([M+H]⁺); IR (thin film) 3368, 3274, 1114, 808cm⁻¹.

Prophetically, compounds CI49-CI57 (Table 1) could be made in accordancewith the procedures disclosed in Example 50.

Example 51 Preparation of3-Chloro-4-((pyridin-2-ylamino)methyl)benzaldehyde (CI58)

To a stirred solution of 4-(bromomethyl)-3-chlorobenzaldehyde (2 g, 9mmol) in N,N-dimethylacetamide

(DMA; 20 mL) was added K₂CO₃ (2.36 g, 17.16 mmol) and 2-aminopyridine(0.84 g, 8.58 mmol), and the reaction mixture was stirred at ambienttemperature for 4 h. The reaction mixture was diluted with H₂O andextracted with EtOAc. The combined organic layer was washed with brine,dried over Na₂SO₄, and concentrated under reduced pressure. The residuewas purified by flash column chromatography (SiO₂, 100-200 mesh; 20%EtOAc in n-Hexane) to afford the title compound as off-white solid (1.05g, 50%): mp 122-123° C.; ¹H NMR (400 MHz, CDCl₃) δ 9.94 (s, 1H), 8.11(s, 1H), 7.88 (s, 1H), 7.72 (d, J=4.8 Hz, 1H), 7.62 (d, J=5.7 Hz, 1H),7.4 (m, 1H), 6.64 (d, J=3.9 Hz, 1H), 6.38 (d, J=6.3 Hz, 1H), 5.04 (br s,1H), 4.71 (s, 2H); ESIMS m/z 246.97 ([M+H]⁺).

Example 52 Preparation of N-(2-Chloro-4-vinylbenzyl)pyridin-2-amine(CI59)

To a stirred solution of3-chloro-4-((pyridin-2-ylamino)methyl)benzaldehyde (1 g, 4. mmol) in1,4-dioxane (20 mL) were added K₂CO₃ (0.84 g, 6.09 mmol) and methyltriphenyl phosphonium bromide (2.17 g, 6.09 mmol) at ambienttemperature. Then the resultant reaction mixture was heated at 100° C.for 18 h. After the reaction was deemed complete by TLC, the reactionmixture was cooled to ambient temperature and filtered, and the obtainedfiltrate was concentrated under reduced pressure. The residue waspurified by flash chromatography (SiO₂, 100-200 mesh; 10% EtOAc inn-Hexane) to afford the title compound as a white solid (0.5 g, 50%): mp119-121° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.12 (s, 1H), 7.42-7.40 (m, 3H),7.26 (s, 1H), 6.66 (m, 2H), 6.36 (d, J=6.3 Hz, 1H), 5.75 (d, J=13.2 Hz,1H), 4.92 (br s, 1H), 4.60 (s, 2H); ESIMS m/z 245.05 ([M+H]⁺).

Example 53 Preparation of Ethyl2-amino-2-(5-bromo-3-chloropyridin-2-yl)acetate (CI60)

Ethyl 2-(diphenylmethyleneamino)acetate (10.2 g, 38.2 mmol) was added tosodium hydride (NaH; 3.18 g, 133.52 mmol) in DMF (50 mL) at 0° C., andthe mixture was stirred for 30 min. To this was added5-bromo-2,3-dichloropyridine (12.9 g, 57.23 mmol), and the reactionmixture was stirred for 3 h at ambient temperature. The reaction mixturewas quenched with 2 N HCl solution and then stirred for 4 h at ambienttemperature. The mixture was extracted with EtOAc. The combined EtOAclayer was washed with brine, dried over anhydrous Na₂SO₄, andconcentrated under reduced pressure. Purification by flash columnchromatography (20-30% EtOAc in hexane) afforded the title compound as aliquid (1.3 g, 20%): ¹H NMR (400 MHz, CDCl₃) δ 8.52 (s, 1H), 7.89 (s,1H), 5.09 (s 1H), 4.23 (m, 2H), 2.27 (br s, 2H), 1.26 (m, 3H); ESIMS m/z293.05 ([M+H]⁺); IR (thin film) 3381, 3306, 1742, 759, 523 cm⁻¹.

Example 54 Preparation of (5-Bromo-3-chloropyridin-2-yl)methanaminehydrochloride (CI61)

A stirred solution of ethyl2-amino-2-(5-bromo-3-chloropyridin-2-yl)acetate (0.5 g, 1.7 mmol) in 3 NHCl (25 mL) was heated at reflux for 4 h. The reaction mixture waswashed with diethyl ether and H₂O. The combined ether layer wasconcentrated under reduced pressure to afford the title compound as anoff-white solid (400 mg, 65%): ¹H NMR (400 MHz, CDCl₃) δ 8.78 (s, 1H),8.70 (br s, 2H), 8.45 (s, 1H), 4.56 (m, 2H); ESIMS m/z 221.15 ([M+H]⁺).

Example 55 Preparation of2-((5-Bromo-3-chloropyridin-2-yl)methyl)isoindoline-1,3-dione (CI62)

To a stirred solution of (5-bromo-3-chloropyridin-2-yl)methanaminehydrochloride (0.3 g, 1.4 mmol) in toluene (40 mL) was added TEA (0.41g, 4.08 mmol) and phthalic anhydride (0.24 g, 1.63 mmol), and thereaction mixture was heated at reflux for 2 h. The reaction mixture wasconcentrated under reduced pressure, and the residue was diluted withH₂O and extracted with EtOAc. The combined EtOAc layer was washed withbrine, dried over anhydrous Na₂SO₄, and concentrated under reducedpressure. The residue was purified by column chromatography (20-30%EtOAc in hexane) to afford the title compound as a white solid (0.25 g,65%): ¹H NMR (400 MHz, CDCl₃) δ 8.78 (s, 1H), 8.45 (s, 1H), 7.88 (m,2H), 7.74 (m, 2H), 4.56 (m, 2H); ESIMS m/z 349 ([M−H]⁻); IR (thin film)3307, 1665, 1114, 813 cm⁻¹.

Example 56 Preparation of2-((3-Chloro-5-vinylpyridin-2-yl)methyl)isoindoline-1,3-dione (CI63)

To a stirred solution of2-((5-bromo-3-chloropyridin-2-yl)methyl)isoindoline-1,3-dione (0.23 g,0.65 mmol) in toluene (10 mL) were added Pd(PPh₃)₄ (3.7 mg, 0.003 mmol),K₂CO₃ (0.269 g, 1.95 mmol) and vinyl boronic anhydride pyridine complex(0.78 g, 3.28 mmol), and the reaction mixture was heated at reflux for16 h. The reaction mixture was filtered, and the filtrate was washedwith H₂O and brine, dried over anhydrous Na₂SO₄, and concentrated underreduced pressure. Purification by flash column chromatography (20-30%EtOAc in hexane) afforded the title compound as an off-white solid (0.2g, 65%): ¹H NMR (400 MHz, CDCl₃) δ 8.30 (s, 1H), 7.91 (m, 2H), 7.77 (m,3H), 7.72 (m, 1H), 6.63 (m, 1H), 5.79 (d, J=16.0 Hz, 1H), 5.39 (d,J=16.0 Hz, 1H), 5.12 (s, 2H); ESIMS m/z 299.20 ([M+H]⁺).

Example 57 Preparation of(E)-2-((3-Chloro-5-(4,4,4-trifluoro-3-(3,4,5-trichloro-phenyl)but-1-en-1-yl)pyridin-2-yl)methyl)isoindoline-1,3-dione(CI64)

To a stirred solution of2-((3-chloro-5-vinylpyridin-2-yl)methyl)isoindoline-1,3-dione (0.35 g,1.17 mmol) in 1,2-dichlorobenzene (10 mL) were added5-(1-bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (0.8 g, 2.3mmol), CuCl (23 mg, 0.12 mmol), 2,2-bipyridyl (0.073 g, 0.234 mmol), andthe reaction mixture was heated at 180° C. for 16 h. The reactionmixture was concentrated under reduced pressure and purified by columnchromatography (20-30% EtOAc in hexane) to afford the title compound asa liquid (0.4 g, 50%): mp 79-82° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.27 (s,1H), 7.91 (m, 2H), 7.77 (m, 3H), 7.36 (s, 2H), 6.51 (d, J=15.6 Hz, 1H),6.32 (dd, J=15.6, 8.0 Hz, 1H), 5.30 (s, 2H), 4.13 (m, 1H); ESIMS m/z 559([M+H]⁺).

Example 58 Preparation of(E)-(3-Chloro-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)pyridin-2-yl)methanamine(CI65)

To a stirred solution of(E)-2-((3-chloro-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)pyridin-2-yl)methyl)isoindoline-1,3-dione(200 mg, 0.358 mmol) in EtOH (5 mL) was added hydrazine hydrate (89.6mg, 1.79 mmol), and the reaction mixture was heated at reflux for 2 h.The reaction mixture was concentrated under reduced pressure, and theresidue was dissolved in CH₂Cl₂. The organic layer was washed with H₂Oand brine, dried over anhydrous Na₂SO₄, and concentrated under reducedpressure to afford the title compound as a solid (100 mg). The productobtained in this reaction was carried on to the next step withoutfurther purification.

Example 59 Preparation of 4-(Bromomethyl)-1-naphthonitrile (CI66)

To a stirred solution of 4-methyl-1-naphthonitrile (5 g, 30 mmol) inCCl₄ (50 mL) under argon atmosphere was added NBS (6.06 g, 34.09 mmol),and the reaction mixture was degassed for 30 min AIBN (0.3 g, 2.1 mmol)was added, and the resultant reaction mixture was heated at reflux for 4h. The reaction mixture was cooled to ambient temperature, diluted withH₂O and extracted with CH₂Cl₂ (3×100 mL). The combined CH₂Cl₂ layer waswashed with brine, dried over Na₂SO₄, and concentrated under reducedpressure. The residue was purified by flash column chromatography (SiO₂,100-200 mesh; 5% EtOAc in n-Hexane) to afford the title compound as awhite solid (3.8 g, 52%): mp 131-133° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.33(m, 1H), 8.24 (m, 1H), 7.88 (d, J=8.0 Hz, 1H), 7.78 (m, 2H), 7.62 (d,J=8.0 Hz, 1H), 4.95 (s, 2H); ESIMS m/z 245.92 ([M+H]⁺); IR (thin film)2217 cm⁻¹.

Example 60 Preparation of 4-(Bromomethyl)-1-naphthaldehyde (CI67)

To a stirred solution of 4-(bromomethyl)-1-naphthonitrile (8 g, 33 mmol)in toluene (100 mL) at 0° C. was added dropwise DIBAL-H (1.0 M solutionin toluene; 43 mL), and the reaction mixture was stirred at 0° C. for 1h. 3 N HCl in H₂O (50 mL) was added to the mixture until it became awhite slurry and then additional 1 N HCl (20 mL) was added. The organiclayer was collected and the aqueous layer was extracted with EtOAc(3×100 mL). The combined organic layer was dried over Na₂SO₄ andconcentrated under reduced pressure. Purification by flash columnchromatography (SiO₂, 100-200 mesh; 5% EtOAc in petroleum ether)afforded the title compound as a white solid (7 g, 88%): mp 115-116° C.;¹H NMR (400 MHz, CDCl₃) δ 10.41 (s, 1H), 9.35 (m, 1H), 8.22 (m, 1H),7.90 (d, J=8.0 Hz, 1H), 7.75 (m, 3H), 4.95 (s, 2H); ESIMS m/z 248.88([M+H]⁺).

Example 61 Preparation of4-((1,3-Dioxoisoindolin-2-yl)methyl)-1-naphthaldehyde (CI68)

To a stirred solution of 4-(bromomethyl)-1-naphthaldehyde (7 g, 28 mmol)in DMF (100 mL) was added potassium phthalimide (7.3 g, 39.5 mmol), andthe mixture was heated at 85° C. for 2 h. The reaction mixture wascooled to ambient temperature and diluted with H₂O (100 mL). Theobtained solid was separated by filtration and dried under vacuum toafford the title compound as a white solid (8.8 g, 98%): mp 190-192° C.;¹H NMR (400 MHz, CDCl₃) δ 10.39 (s, 1H), 9.25 (m, 1H), 8.41 (m, 1H),8.10 (d, J=8.0 Hz, 1H), 7.95 (m, 4H), 7.80 (m, 4H), 7.61 (m, 4H), 5.39(s, 2H); ESIMS m/z 316.09 ([M+H]⁺); IR (thin film) 1708 cm⁻¹.

Example 62 Preparation of 2-((4-Vinylnaphthalen-1-yl)methyl)isoindoline-1,3-dione (CI69)

To a stirred solution of4-((1,3-dioxoisoindolin-2-yl)methyl)-1-naphthaldehyde (9 g, 28.5 mmol)in 1,4-dioxane (100 mL) were added K₂CO₃ (6 g, 42.8 mmol) and methyltriphenyl phosphonium bromide (15.3 g, 35.7 mmol) at ambienttemperature. The reaction mixture was heated at 100° C. for 14 h andthen was cooled to ambient temperature. The reaction mixture wasfiltered, and the obtained filtrate was concentrated under reducedpressure. Purification by flash chromatography (SiO₂, 100-200 mesh; 20%EtOAc in petroleum ether) afforded the title compound as a white solid(6 g, 67%): mp 146-147° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.35 (m, 2H), 7.95(m, 4H), 7.65 (m, 4H), 7.39 (m, 1H), 5.81 (m, 1H), 5.45 (m, 1H), 5.21(s, 2H); ESIMS m/z 314.13 ([M+H]⁺).

Example 63 Preparation of(E)-2-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-1-yl)methyl)isoindoline-1,3-dione(CI70)

To a stirred solution of2-((4-vinylnaphthalen-1-yl)methyl)isoindoline-1,3-dione (1.5 g, 4.79mmol) in 1,2-dichlorobenzene (15 mL) were added1-(1-bromo-2,2,2-trifluoroethyl)-3,4,5-trichlorobenzene (3.2 g, 9.5mmol), CuCl (24 mg, 0.24 mmol) and 2,2-bipyridyl (0.149 g, 0.95 mmol),and the resultant reaction mixture was degassed with argon for 30 minand then stirred at 180° C. for 14 h. After the reaction was deemedcomplete by TLC, the reaction mixture was cooled to ambient temperatureand filtered, and the filtrate was concentrated under reduced pressure.Purification by flash chromatography (SiO₂, 100-200 mesh; 25-30% EtOAcin petroleum ether) afforded the title compound as an off-white solid(1.5 g, 56%): mp 158-160° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.40 (m, 1H),7.89 (m, 2H), 7.74 (m, 2H), 7.64 (m, 2H), 7.58 (m, 2H), 7.46 (s, 2H),7.36 (m, 2H), 6.31 (m, 1H), 5.30 (s, 2H), 4.21 (m, 1H); ESIMS m/z 572.08([M−H]⁻).

Example 64 Preparation of(E)-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-1-yl)methanamine(CI71)

To a stirred solution of(E)-2-((4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-1-yl)methyl)isoindoline-1,3-dione(0.4 g, 0.7 mmol) in EtOH was added hydrazine hydrate (0.18 g, 3.5mmol), and the resultant reaction mixture was heated at 80° C. for 2 h.The reaction mixture was filtered, and the filtrate was concentrated.The residue was dissolved in CH₂Cl₂, and the solution was washed withbrine, dried over Na₂SO₄, and concentrated under reduced pressure. Thetitle compound was isolated as a gummy liquid (150 mg, 50%). The productobtained in this reaction was carried on to the next step withoutfurther purification.

Example 65 Preparation of 2-((4-Bromophenyl)amino)isoindoline-1,3-dione(CI72)

To a stirred solution of (4-bromophenyl)hydrazine hydrochloride (0.5 g,2.2 mmol) in glacial acetic acid (8 mL) was added phthalic anhydride(0.398 g, 2.690 mmol), and the reaction mixture was stirred at 130° C.for 1 h under a nitrogen atmosphere. The reaction mixture was quenchedwith satd aq. NaHCO₃ solution and filtered to give a solid. Purificationby column chromatography (SiO₂, 0-10% EtOAc in petroleum ether) affordedthe title compound as a solid (60 mg, 84%): mp 205-206° C.; ¹H NMR (400MHz, CDCl₃) δ 8.71 (s, 1H), 7.99 (m, 4H), 7.32 (d, J=8.8 Hz, 2H), 6.79(d, J=8.8 Hz, 2H); ESIMS m/z 314.95 ([M−H]⁻).

Example 66 Preparation of 2-((4-Vinylphenyl)amino)isoindoline-1,3-dione(CI73)

To a solution of 2-(4-bromophenylamino)isoindoline-1,3-dione (2 g, 6mmol) in 1,2-dimethoxyethane (20 mL) and H₂O (4 mL) were added vinylboronic anhydride pyridine complex (4.57 g, 18.98 mmol) and K₂CO₃ (1.3g, 9.5 mmol) followed by Pd(PPh₃)₄ (0.219 g, 0.189 mmol). The resultantreaction mixture was heated at 150° C. in a microwave for 30 min andthen was concentrated under reduced pressure. Purification by columnchromatography (SiO₂, 15% EtOAc in petroleum ether) afforded the titlecompound as a solid (200 mg, 13%): mp 174-176° C.; ¹H NMR (400 MHz,CDCl₃) δ 8.65 (s, 1H), 7.94 (m, 4H), 7.29 (d, J=8.4 Hz, 2H), 6.72 (d,J=8.4 Hz, 2H), 6.61 (m, 1H), 5.61 (d, J=17.6 Hz, 1H), 5.05 (d, J=11.2Hz, 1H); ESIMS m/z 263.18 ([M−H]⁻).

Example 67 Preparation of(E)-2-((4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)amino)isoindoline-1,3-dione(CI74)

To a stirred solution of 2-(4-vinylphenylamino)isoindoline-1,3-dione(0.3 g, 1.1 mmol) in 1,2-dichlorobenzene (5 mL) were added CuCl (0.022g, 0.273 mmol), 2,2-bipyridyl (0.07 g, 0.46 mmol) and5-(1-bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (0.77 g, 2.27mmol). The reaction mixture was degassed with argon for 30 min and washeated at 180° C. for 2 h. The reaction mixture was then concentratedunder reduced pressure, and the residue was purified by columnchromatography (SiO₂, O-30% EtOAc in petroleum ether) to afford thetitle compound as a solid (450 mg, 75%): mp 187-189° C.; ¹H NMR (400MHz, CDCl₃) δ 8.75 (s, 1H), 7.96 (m, 4H), 7.82 (s, 2H), 7.37 (d, J=8.8Hz, 1H), 6.73 (d, J=8.4 Hz, 2H), 6.61 (m, 2H), 6.58 (m, 1H), 4.59 (m,1H); ESIMS m/z 523.05 ([M−H]⁻).

Example 68 Preparation of(E)-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)hydrazine(CI75)

To a stirred solution of(E)-2-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)phenylamino)isoindoline-1,3-dione (0.16 g, 0.31 mmol) in EtOH (5 mL), was addedhydrazine hydrate (0.076 g, 1.52 mmol), and the reaction mixture washeated at 85° C. for 1 h. The reaction mixture was cooled to ambienttemperature and filtered, and the filtrate was concentrated underreduced pressure to afford the title compound as a solid (0.08 g, 66%)which was carried on to the next step without further purification.

Example 69 Preparation of 2-(4-Vinylphenoxy)isoindoline-1,3-dione (CI76)

To a stirred solution of 4-vinylphenylboronic acid (2 g, 13 mmol),2-hydroxyisoindoline-1,3-dione (3.63 g, 24.53 mmol), and CuCl (1.214 g12.26 mmol) in 1,2-dichloroethane (50 mL) was added pyridine (1.065 g,13.48 mmol), and the resultant reaction mixture was stirred at ambienttemperature for 48 h. The reaction mixture was diluted with H₂O andextracted with CHCl₃. The combined CHCl₃ layer was washed with brine,dried over Na₂SO₄ and concentrated under reduced pressure. Purificationby flash column chromatography (SiO₂; 20% EtOAc in petroleum ether)afforded the title compound as a white solid (2 g, 63%): mp 129-131° C.;¹H NMR (400 MHz, CDCl₃) δ 7.93 (d, J=2.0 Hz, 2H), 7.82 (d, J=3.2 Hz,2H), 7.38 (d, J=2.0 Hz, 2H), 7.14 (d, J=2.0 Hz, 2H), 6.70 (m, 1H), 5.83(d, J=16.0 Hz, 1H), 5.22 (d, J=10.8 Hz, 1H); ESIMS m/z 266.12 ([M+H]⁺).

Example 70 Preparation of(E)-2-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenoxy)isoindoline-1,3-dione(CI77)

To a stirred solution of 2-(4-vinylphenoxy)isoindoline-1,3-dione (0.3 g,1.1 mmol) in 1,2-dichlorobenzene (10 mL) was added1-(1-bromoethyl)-3,4,5-trichlorobenzene (769 mg, 2.26 mmol), CuCl (22mg, 0.22 mmol) and 2,2-bipyridyl (35 mg, 0.44 mmol), and the resultantreaction mixture was degassed with argon for 30 min and heated to 180°C. for 24 h. The reaction mixture was cooled to ambient temperature andfiltered, and the filtrate was concentrated under reduced pressure. Thecrude material was purified by column chromatography (SiO₂, 100-200mesh; 20% EtOAc in petroleum ether) to afford the title compound as asolid (0.29 g, 50%): ¹H NMR (400 MHz, CDCl₃) δ 7.90 (m, 1H), 7.62 (m,2H), 7.50 (m, 1H), 7.40 (s, 2H), 7.12 (s, 1H), 6.90 (m, 2H), 6.60 (m,2H), 6.20 (m, 1H), 4.08 (m, 1H); ESIMS m/z 524.09 ([M−H]⁻).

Example 71 Preparation of(E)-O-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)hydroxylamine(CI78)

To a stirred solution of(E)-2-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)phenoxy)isoindoline-1,3-dione (0.2 g, 0.4 mmol) in EtOH was added hydrazinehydrate (0.1 g, 1.9 mmol), and the resultant reaction mixture was heatedat 90° C. for 1 h. The reaction mixture was filtered, and the filtratewas concentrated. The residue was dissolved in CH₂Cl₂. washed withbrine, dried over Na₂SO₄ and concentrated under reduced pressure toafford the crude title compound as a gummy liquid (0.08 g, 53%): ¹H NMR(400 MHz, CDCl₃) δ 7.40 (s, 2H), 6.98 (s, 1H), 6.82 (s, 2H), 6.48 (m,1H), 6.20 (m, 1H), 5.02 (s, 1H), 4.08 (m, 1H); ESIMS m/z 394.94([M−H]⁻).

Example 72 Preparation of(E)-N-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)benzyl)acetamide(CC1)

To a stirred solution of(E)-(2-chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine (0.3 g, 0.8 mmol) in CH₂Cl₂ (10 mL) was added aceticanhydride (0.12 mL, 1.14 mmol), and TEA (0.217 mL, 1.52 mmol), and theresultant reaction mixture was stirred at ambient temperature for 6 h.The reaction mixture was diluted with H₂O and extracted with CH₂Cl₂. Thecombined CH₂Cl₂ layer was washed with brine, dried over Na₂SO₄, andconcentrated under reduced pressure. Purification by flash columnchromatography (SiO₂, 100-200 mesh; 30-50% ethyl acetate in hexane)afforded the title compound as an off-white solid (0.2 g, 60%) mp107-109° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.37 (m, 3H), 7.28 (m, 4H), 6.60(d, J=16.0 Hz, 1H), 6.36 (dd, J=16.0, 8.0 Hz, 1H), 5.75 (br s, 1H), 4.46(d, J=6 Hz, 2H), 4.01 (m, 1H), 2.11 (s, 3H); ESIMS m/z 402.00 ([M+H]⁺).

Compounds CC2-CC6 in Table 1 were made in accordance with the proceduresdisclosed in Example 72. In addition, compound DC56 in Table 1 was madefrom compound DC55 in accordance with the procedures disclosed inExample 72.

Example 73 Preparation of(E)-N-(2-Chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)acetamide(CC7)

To a stirred solution of(E)-(2-chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine(0.3 g, 0.8 mmol) in DMF (5 mL) was added 2,2,2-trifluoro-propanoic acid(97 mg, 0.76 mmol), HOBt.H₂O (174 mg, 1.14 mmol) and EDC.HCl (217 mg,1.14 mmol) and DIPEA (196 mg, 1.52 mmol), and the resultant reactionmixture was stirred at ambient temperature for 18 h. The reactionmixture was diluted with H₂O and extracted with EtOAc. The combinedEtOAc layer was washed with brine, dried over Na₂SO₄, and concentratedunder reduced pressure. Purification by flash column chromatography(SiO₂, 100-200 mesh; ethyl acetate in hexane (30-50% afforded the titlecompound as an off-white solid (0.2 g, 60%): mp 127-128° C.; ¹H NMR (400MHz, CDCl₃) δ 7.42 (m, 4H), 7.24 (m, 2H), 6.53 (d, J=16.0 Hz, 1H), 6.36(dd, J=16.0, 8.0 Hz, 1H), 5.86 (br s, 1H), 4.51 (d, J=6.0 Hz, 2H), 4.05(m, 1H), 2.02 (s, 3H); ESIMS m/z 436.03 ([M+H]⁺).

Compounds CC8-CC28 in Table 1 were made in accordance with theprocedures disclosed in Example 73.

Example 74 Preparation of(E)-N-(Pyridin-2-ylmethyl)-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)benzyl)cyclopropanecarboxamide(CC29)

Step 1:(E)-1-(Pyridin-2-yl)-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)benzyl)methanamine

(E)-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)phenyl)methanamine(0.46 g, 1 mmol) was dissolved in MeOH (3 mL). To this was addedpyridine-2-carbaldehyde (0.107 g, 1 mmol). The reaction mixture wasstirred for 1 h. After 1 h, NaBH₄ (0.076 g, 2 mmol) was added and leftat ambient temperature for 3 h. The reaction mixture was concentrated togive an oily residue. Purification by flash column chromatography (SiO₂,100-200 mesh; 30-50% EtOAc in hexane) afforded the title compound as apale yellow liquid (0.22 g, 40%): ¹H NMR (400 MHz, CDCl₃) δ 8.58 (d,J=4.8 Hz, 1H), 7.74 (m, 1H), 7.62 (m, 2H), 7.52 (m, 1H), 7.4 (s, 2H),7.3 (m, 1H), 7.2 (m, 2H), 6.60 (d, J=16.0 Hz, 1H), 6.38 (dd, J=16.0, 8.0Hz, 1H), 4.10 (m, 1H), 4.02 (s, 2H), 3.96 (s, 2H); ESIMS m/z 552.95([M+H]⁺); IR (thin film) 3338, 1114, 808 cm⁻¹.

Step 2:(E)-N-(Pyridin-2-ylmethyl)-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)benzyl)cyclopropanecarboxamide

(E)-1-(Pyridin-2-yl)-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzyl)methanamine(0.27 g, 0.05 mmol) was taken up in CH₂Cl₂ (3 mL). To this was added TEA(0.14 mL, 0.1 mmol). The reaction mixture was stirred for 10 min After10 min, the reaction mixture was cooled to 0° C., andcyclopropylcarbonyl chloride (0.08 mL, 0.075 mmol) was added. Thereaction mixture was stirred at ambient temperature for 1 h and then waswashed with H₂O and satd aq NaHCO₃ solution. The organic layer was driedover anhydrous Na₂SO₄ and evaporated to obtain pale yellow gummymaterial (0.15 g, 50%): ¹H NMR (400 MHz, CDCl₃) δ 8.58 (d, J=4.6 Hz,1H), 7.74 (m, 1H), 7.62 (m, 2H), 7.52 (m, 1H), 7.4 (s, 2H), 7.3 (m, 1H),7.2 (m, 2H), 6.60 (d, J=16.0 Hz, 1H), 6.38 (dd, J=16.0, 8.0 Hz, 1H),5.02 (s, 1H), 4.8 (s, 1H), 4.8 (d, J=10 Hz, 2H), 4.10 (m, 1H), 1.8 (m,1H), 1.2 (m, 2H), 0.6 (m, 2H); ESIMS m/z 620.86 ([M−H]⁻); IR (thin film)1645, 1115, 808 cm⁻¹.

Example 75 Preparation of(E)-N-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)-3-(methylsulfonyl)propanamide(CC30)

(E)-N-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)-3-(methylthio)propanamide(0.15 g, 0.28 mmol) was treated with oxone (0.175 g, 0.569 mmol) in 1:1acetone:water (20 mL) for 4 h at ambient temperature. The acetone wasevaporated to obtain a white solid (0.095 g, 60%): mp 101-104° C.; ¹HNMR (400 MHz, CDCl₃) δ 7.41 (m, 4H), 7.24 (m, 1H), 6.53 (d, J=16.0 Hz,1H), 6.35 (dd, J=16.0, 8.0 Hz, 1H), 6.12 (br s, 1H), 4.53 (m, 2H), 4.10(m, 1H), 3.42 (m, 2H), 2.91 (s, 3H), 2.78 (m, 2H); ESIMS m/z 559.75([M−H]⁻).

Example 76 Preparation of(E)-1-(2-Chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)-3-ethylurea(CC31)

To a stirred solution of(E)-(2-chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine(0.2 g, 0.5 mmol) in CH₂Cl₂ (5 mL) at 0° C. were added TEA (0.141 mL, 1mmol) and ethylisocyanate (0.053 g, 0.75 mmol), and the reaction mixturewas stirred for 1 h at 0° C. The reaction mixture was diluted withCH₂Cl₂. The organic layer was washed with H₂O and brine, dried overNa₂SO₄, and concentrated under reduced pressure. Purification by columnchromatography (SiO₂, 100-200 mesh; 30-50% EtOAc in hexane) afforded thetitle compound as a solid (0.141 g, 60%): mp 177-178° C.; ¹H NMR (400MHz, CDCl₃) δ 7.58 (m, 2H), 7.41 (m, 3H), 7.24 (m, 1H), 6.53 (d, J=16.0Hz, 1H), 6.35 (dd, J=16.0, 8.0 Hz, 1H), 4.70 (br s, 1H), 4.43 (s, 2H),4.08 (m, 1H), 3.21 (m, 2H), 1.25 (m, 3H); ESIMS m/z 463 ([M−H]⁻).

Compounds CC32-CC35 in Table 1 were made in accordance with theprocedures disclosed in Example 76.

Example 77 Preparation of(E)-3-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)-1,1-dimethylurea(CC36)

To a stirred solution of(E)-(2-chloro-4-(3-(3,4,5-trichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine(0.2 g, 0.5 mmol) in CH₂Cl₂ (5 mL) at 0° C. were added TEA (0.141 mL, 1mmol) and N,N-dimethylcarbamoyl chloride (0.08 g, 0.075 mmol), and thereaction mixture was stirred for 1 h at 0° C. The reaction mixture wasdiluted with CH₂Cl₂. The organic layer was washed with H₂O and brine,dried over Na₂SO₄, and concentrated under reduced pressure. Purificationby column chromatography (SiO₂, 100-200 mesh; 30-50% EtOAc in hexane)afforded the title compound as a solid (0.15 g, 60%): ¹H NMR (400 MHz,CDCl₃) δ 7.39 (m, 4H), 7.28 (m, 1H), 6.54 (d, J=16.0 Hz, 1H), 6.34 (dd,J=16.0, 8.0 Hz, 1H), 4.97 (br s, 1H), 4.38 (d, J=6.0 Hz, 2H), 4.10 (m,1H), 2.9 (s, 3H), 2.7 (s, 3H); ESIMS m/z 497 ([M−H]⁻); IR (thin film)3350, 1705, 1114, 808 cm⁻¹.

Example 78 Preparation of(E)-1-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)-3-ethylthiourea(CC37)

To a stirred solution of(E)-(2-chloro-4-(3-(3,4,5-trichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine(0.2 g, 0.5 mmol) in CH₂Cl₂ (5 mL) at 0° C. were added TEA (0.141 mL, 1mmol) and ethyl isothicyanate (0.053 g, 0.75 mmol), and the reactionmixture was stirred for 1 h at 0° C. The reaction mixture was dilutedwith CH₂Cl₂. The organic layer was washed with H₂O and brine, dried overNa₂SO₄, and concentrated under reduced pressure. Purification by columnchromatography (SiO₂, 100-200 mesh; 30-50% EtOAc in hexane) afforded thetitle compound as a solid (0.14 g, 60%): mp 88-91° C.; ¹H NMR (400 MHz,CDCl₃) δ 7.49 (d, J=8 Hz, 1H), 7.41 (d, J=7.2 Hz, 2H), 7.26 (m, 2H),6.50 (d, J=16 Hz, 1H), 6.35 (dd, J=16.0, 8.0 Hz, 1H), 6.0 (br s, 1H),5.73 (br s, 1H), 4.80 (br s, 2H), 4.09 (m, 1H), 1.23 (m, 3H); ESIMS m/z515.01 ([M+H]⁺).

Compound CC38 in Table 1 was made in accordance with the proceduresdisclosed in Example 78.

Example 79 Preparation of (E)-tert-Butyl(2-chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)-3-ethylurea(CC39)

To a stirred solution of(E)-(2-chloro-4-(3-(3,4,5-trichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine(0.2 g, 0.5 mmol in CH₂Cl₂ (5 mL) at 0° C. were added TEA (0.141 mL, 1mmol) and di-tert-butyl dicarbonate (0.163 mL, 0.75 mmol), and thereaction mixture was stirred for 4 h at ambient temperature. Thereaction mixture was diluted with CH₂Cl₂. The organic layer was washedwith H₂O and brine, dried over Na₂SO₄, and concentrated under reducedpressure. Purification by column chromatography (SiO₂, 100-200 mesh;10-20% EtOAc in hexane) afforded the title compound as a white solid(0.147 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.39 (m, 4H), 7.28 (m, 1H),6.54 (d, J=16.0 Hz, 1H), 6.34 (dd, J=16.0, 8.0 Hz, 1H), 4.97 (br s, 1H),4.38 (d, J=6.0 Hz, 2H), 4.10 (m, 1H), 1.53 (s, 9H); ESIMS m/z 526.09([M−H]⁻); IR (thin film) 3350, 1705, 1114, 808 cm⁻¹.

Compound CC40 in Table 1 was made in accordance with the proceduresdisclosed in Example 79.

Example 80 Preparation of (E)-Methyl2-((2-chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)amino)-2-oxoacetate(CC41)

To a stirred solution of(E)-(2-chloro-4-(3-(3,4,5-trichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine(0.2 g, 0.5 mmol) in CH₂Cl₂ (5 mL) at 0° C. were added TEA (0.141 mL, 1mmol) and methyl 2-chloro-2-oxoacetate (0.09 g, 0.75 mmol), and thereaction mixture was stirred for 1 h at 0° C. The reaction mixture wasdiluted with CH₂Cl₂. The organic layer was washed with H₂O and brine,dried over Na₂SO₄, and concentrated under reduced pressure. Purificationby column chromatography (SiO₂, 100-200 mesh; 20% EtOAc in hexane)afforded the title compound as a solid (0.12 g, 50%): ¹H NMR (400 MHz,CDCl₃) δ 7.48 (m, 1H). 7.43 (m, 3H), 7.38 (m, 1H), 7.23 (s, 1H), 6.55(d, J=16.0 Hz, 1H), 6.36 (dd, J=16.0, 8.0 Hz, 1H), 4.60 (d, J=4.4 Hz,2H), 4.18 (m, 1H), 3.85 (s, 3H); ESIMS m/z 512.22 ([M−H]⁻); IR (thinfilm) 1740, 1701, 1114, 808 cm⁻¹.

Example 81 Preparation of(E)-N¹-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)-N²-(2,2,2-trifluoroethyl)oxalamide(CC42)

To a stirred solution of 2,2,2-trifluoroethylamine hydrochloride (0.1 g,0.77 mmol) in CH₂Cl₂ (10 mL) was added dropwise trimethylaluminum (2 Msolution in toluene; 0.39 mL, 0.77 mmol), and the reaction mixture wasstirred at 25° C. for 30 min A solution of (E)-methyl2-((2-chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)-2-oxoacetate(0.2 g, 0.38 mmol) in CH₂Cl₂ (5 mL) was added dropwise to the reactionmixture at 25° C. The reaction mixture was stirred at reflux for 18 h,cooled to 25° C., quenched with 0.5 N HCl solution (50 mL) and extractedwith EtOAc (2×50 mL). The combined organic extracts were washed withbrine, dried over Na₂SO₄, and concentrated under reduced pressure. Thecrude compound was purified by flash chromatography (SiO₂, 100-200 mesh;20%-40% EtOAc in n-hexane) to afford the title compound (0.13 g, 60%):mp 161-163° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 9.45 (br s, 2H), 7.90 (s,2H), 7.75 (s, 1H), 7.46 (s, 1H), 7.28 (s, 1H), 6.93 (m, 1H), 6.75 (m,1H), 4.80 (m, 1H), 4.40 (s, 2H), 3.90 (s, 2H); ESIMS m/z 578.96([M−H]⁻).

Example 82 Preparation of(E)-N-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)pyridin-2-amine(CC43)

To a stirred solution of N-(2-chloro-4-vinylbenzyl)pyridin-2-amine (0.3g, 1.22 mmol) in 1,2-dichlorobenzene (5 mL) were added5-(1-bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (0.83 g, 2.44mmol), CuCl (24 mg, 0.24 mmol) and 2,2-bipyridyl (76 mg, 0.48 mmol). Theresultant reaction mixture was degassed with argon for 30 min and thenstirred at 180° C. for 24 h. After the reaction was deemed complete byTLC, the reaction mixture was cooled to ambient temperature andfiltered, and the filtrate was concentrated under reduced pressure.Purification by flash chromatography (SiO₂, 100-200 mesh; 15% EtOAc inn-hexane) afforded the title compound as an off-white solid (0.2 g,35%): mp 140-142° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.11 (d, J=4.0 Hz, 1H),7.40 (m, 5H), 7.22 (m, 1H), 6.61 (m, 2H), 6.35 (m, 2H), 4.94 (br s, 1H),4.61 (d, J=6.4 Hz, 2H), 4.11 (m, 1H); ESIMS m/z 505.39 ([M+H]⁺).

Example 83 Preparation of(E)-N-((3-Chloro-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)-but-1-en-1-yl)pyridin-2-yl)methyl)-3,3,3-trifluoropropanamide(CC44)

To a stirred solution of(E)-(3-chloro-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)pyridin-2-yl)methanamine(0.1 g, 0.2 mmol) in CH₂Cl₂ (5 mL) were added 3,3,3-trifluoropropanoicacid (45 mg, 0.350 mmol), EDC.HCl (67 mg, 0.350 mmol), HOBt.H₂O (71 mg,0.467 mmol) and DIPEA (60.2 mg, 0.467 mmol), and the reaction mixturewas stirred at ambient temperature for 18 h. The reaction mixture wasdiluted with CH₂Cl₂ and washed with H₂O. The combined CH₂Cl₂ layer waswashed with brine, dried over anhydrous Na₂SO₄, and concentrated underreduced pressure. Purification by flash column chromatography (SiO₂,100-200 mesh; 15% EtOAc in petroleum ether) afforded the title compoundas a pale yellow liquid (30 mg, 35%): ¹H NMR (400 MHz, CDCl₃) δ 8.41 (s,1H), 7.77 (s, 1H), 7.47 (br s, 1H), 7.40 (s, 2H), 6.58 (d, J=16.0 Hz,1H), 6.45 (dd, J=16.0, 8.0 Hz, 1H), 4.68 (d, J=4.0 Hz, 2H), 4.14 (m,1H), 3.24 (q, J=10.8 Hz, 2H); ESIMS m/z 536.88 ([M−H]⁻); IR (thin film)3320, 1674, 1114, 808.

Compound CC45 in Table 1 was made in accordance with the proceduresdisclosed in Example 83.

Example 84 Preparation of(E)-3,3,3-Trifluoro-N-((4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-1-yl)methyl)propanamide(CC46)

To a stirred solution of(E)-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-1-yl)methanamine(0.1 g, 0.22 mmol) in CH₂Cl₂ (8 mL) were added 3,3,3-trifluoropropanoicacid (0.032 g, 0.24 mmol), HOBt.H₂O (52 mg, 0.33 mmol), EDC.HCl (0.065g, 0.33 mmol) and DIPEA (0.044 g, 0.45 mmol), and the resultant reactionmixture was stirred at ambient temperature for 18 h. The reactionmixture was diluted with H₂O and extracted with EtOAc (3×30 mL). Thecombined EtOAc layer was washed with brine, dried over Na₂SO₄, andconcentrated under reduced pressure. Purification by flash columnchromatography (SiO₂, 100-200 mesh; 15% EtOAc in n-hexane) afforded thetitle compound as a gummy material (60 mg, 50%): mp 151-153° C.; ¹H NMR(400 MHz, CDCl₃) δ 8.06 (m, 1H), 7.61 (m, 4H), 7.48 (s, 2H), 7.44 (d,J=8.0 Hz, 1H), 7.38 (m, 1H), 6.42 (m, 1H), 5.92 (br s, 1H), 4.92 (m,2H), 4.24 (m, 1H), 3.12 (m, 2H); ESIMS m/z 554.04 ([M−H]⁻).

Compounds CC47-CC48 in Table 1 were made in accordance with theprocedures disclosed in Example 84.

Example 85 Preparation of(E)-1-Ethyl-34(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-1-yl)methyl)urea(CC49)

To a stirred solution of(E)-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-1-yl)methanamine(0.1 g, 0.22 mmol) in CH₂Cl₂ at 0° C. were added TEA (0.064 mL, 0.44mmol) and ethylisocyanate (0.023 mL, 0.33 mmol), and the reactionmixture was stirred for 1 h at 0° C. The reaction mixture was dilutedwith CH₂Cl₂. The organic layer was washed with H₂O and brine, dried overNa₂SO₄, and concentrated under reduced pressure. Purification by columnchromatography (SiO₂, 100-200 mesh; 30% EtOAc in hexane) afforded thetitle compound as a solid (0.07 g, 60%): mp 84-87° C.; ¹H NMR (400 MHz,CDCl₃) δ 8.06 (m, 1H), 7.98 (m, 1H), 7.61 (m, 3H), 7.48 (s, 2H), 7.44(d, J=8.0 Hz, 1H), 7.38 (m, 2H), 6.42 (m, 1H), 4.92 (s, 2H), 4.6 (br s,1H), 4.24 (m, 1H), 3.21 (m, 2H), 1.2 (t, J=4.6 Hz, 3H); ESIMS m/z 515.33([M+H]⁺).

Example 86 Preparation of(E)-N′-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)cyclopropanecarbohydrazide(CC50)

To a stirred solution of(E)-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)hydrazine(0.1 g, 0.3 mmol) in CH₂Cl₂ (10 mL) was added DIPEA (65 mg, 0.51 mmol),HOBt.H₂O (59 mg, 0.38 mmol), EDC.HCl (73 mg, 0.38 mmol) andcyclopropanecarbonyl chloride (0.024 g, 0.28 mmol), and the reactionmixture was stirred at ambient temperature for 1 h. The reaction mixturewas diluted with satd aq NaHCO₃ solution and extracted with CH₂Cl₂. Thecombined CH₂Cl₂ layer was washed with brine, dried over anhydrousNa₂SO₄, and concentrated under reduced pressure. Purification by flashcolumn chromatography (SiO₂; 5-25% EtOAc in petroleum ether) affordedthe title compound as a solid (65 mg, 55%): mp 138-140° C.; ¹H NMR (400MHz, CDCl₃) δ 9.81 (s, 1H), 7.90 (s, 1H), 7.84 (s, 2H), 7.34 (d, J=8.4Hz, 2H), 6.65 (d, J=15.6 Hz, 1H), 6.61 (m, 1H), 6.57 (s, 1H), 6.48 (dd,J=15.6, 8.8 Hz, 1H), 4.74 (m, 1H), 1.64 (m, 1H), 0.75 (m, 4H); ESIMS m/z461.32 ([M−H]⁻).

Compound CC51 in Table 1 was made in accordance with the proceduresdisclosed in Example 86.

Example 87 Preparation of(E)-N-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenoxy)cyclopropanecarboxamide(CC52)

To a stirred solution of(E)-O-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)hydroxylamine(0.15 g, 0.38 mmol) in CH₂Cl₂ (5 mL) was added EDC.HCl (0.109 g, 0.569mmol), HOBt.H₂O (0.087 g, 0.569 mmol), DIPEA (0.097 g, 0.758 mmol) andcyclopropanecarboxylic acid (0.049 g, 0.569 mmol). The resultantreaction mixture was stirred at ambient temperature for 18 h. Thereaction mixture was diluted with H₂O and extracted with CHCl₃ (35 mL)The combined CHCl₃ layer was washed with brine, dried over Na₂SO₄ andconcentrated under reduced pressure. Purification by flash columnchromatography (SiO₂; 20% EtOAc in hexane) afforded the title compoundas a brown liquid (0.06 g, 34%): ¹H NMR (400 MHz, CDCl₃) δ 7.40 (s, 2H),7.18 (s, 1H), 7.08 (s, 1H), 6.85 (m, 1H), 6.45 (m, 1H), 6.65 (m, 1H),6.20 (m, 1H), 5.55 (s, 1H), 4.08 (m, 1H), 1.90 (m, 1H), 1.30-1.10 (m,4H); ESIMS m/z 464.87 ([M−H]⁻).

Compound CC53 in Table 1 was made in accordance with the proceduresdisclosed in Example 87.

Example 88 Preparation of(Z)-3,3,3-Trifluoro-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)propanamide(CC54)

A silicon borate vial was charged with(E)-3,3,3-trifluoro-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)propanamide(133 mg, 0.269 mmol) and dimethyl sulfoxide (DMSO; 10 mL). The mixturewas placed within 0.6 to 1 meter (m) of a bank of eight 115 wattSylvania FR48T12/350BL/VHO/180 Fluorescent Tube Black Lights and four115 watt Sylvania (daylight) F48T12/D/VHO Straight T12 Fluorescent TubeLights for 72 h. The mixture was concentrated in vacuo and purified byreverse phase chromatography to give the title compound as a colorlessoil (11 mg, 8%): ¹H NMR (300 MHz, CDCl₃) δ 7.28 (s, 2H), 7.25 (m, 2H),7.10 (d, J=8.0 Hz, 2H), 6.89 (d, J=11.4 Hz, 1H), 6.07 (br s, 1H), 6.01(m, 1H), 4.51 (d, J=5.8 Hz, 2H), 4.34 (m, 1H), 3.12 (q, J=7.5 Hz, 2H);¹³C NMR (101 MHz, CDCl₃) δ 162.44, 137.20, 135.38, 135.23, 134.82,134.68, 131.71, 129.00, 128.80, 128.69, 128.10, 127.96, 122.63, 76.70,47.33 (q, J=28 Hz), 43.59, 42.12 (q, J=30 Hz); ESIMS m/z 504 ([M+H]⁺).

Compounds DC46, AC93. AC94 in Table 1 were made in accordance with theprocedures disclosed in Example 88.

Example 89 Preparation of1-(1-Bromo-2,2,2-trifluoroethyl)-3-chlorobenzene (DI2)

The title compound was synthesized in two steps via1-(3-chlorophenyl)-2,2,2-trifluoroethanol (DI1, prepared as in Step 1,Method B in Example 1); isolated as a colorless viscous oil (1.5 g,75%): ¹H NMR (400 MHz, CDCl₃) δ 7.50 (s, 1H), 7.42-7.35 (m, 3H), 5.02(m, 1H), 2.65 (br s, 1H)) and Step 2 in Example 1 and isolated (0.14 g,22%): ¹H NMR (400 MHz, CDCl₃) δ 7.50 (br s, 1H), 7.42-7.35 (m, 3H), 5.07(m, 1H).

The following compounds were made in accordance with the proceduresdisclosed in Example 89.

(1-Bromo-2,2,2-trifluoroethyl)benzene (DI4)

2,2,2-Trifluoro-1-phenylethanol (DI3) was isolated (10 g, 80%): ¹H NMR(300 MHz, CDCl₃) δ 7.48 (m, 2H), 7.40 (m, 3H), 5.02 (m, 1H), 2.65 (d,J=7.1 Hz, 1H). The title compound (DI4) was isolated as a liquid (8.0 g,60%): ¹H NMR (400 MHz, CDCl₃) δ 7.50 (m, 2H), 7.40 (m, 3H), 5.00 (q,J=7.5 Hz, 1H).

1-(1-Bromo-2,2,2-trifluoroethyl)-3,5-dimethylbenzene (DI20)

1-(3,5-Dimethylphenyl)-2,2,2-trifluoroethanol (DI19) was isolated an offwhite solid: ¹H NMR (400 MHz, CDCl₃) δ 7.05 (s, 2H), 7.02 (s, 1H), 4.95(m, 1H), 2.32 (s, 6H); ESIMS m/z 204 GMT). The title compound (DI20) wasisolated (3.0 g, 51%).

1-(1-Bromo-2,2,2-trifluoroethyl)-2,4-dichlorobenzene (DI22)

1-(2,4-Dichlorophenyl)-2,2,2-trifluoroethanol (DI21) was isolated as anoff white powder (5.3 g, 61%): mp 49-51° C.; ¹H NMR (400 MHz, CDCl₃) δ7.62-7.66 (d, 1H), 7.42-7.44 (d, 1H), 7.32-7.36 (d, 1H), 5.6 (m, 1H),2.7 (s, 1H); ESIMS m/z 244 ([M]⁺). The title compound (DI22) wasisolated (3.2 g, 50%): ¹H NMR (400 MHz, CDCl₃) δ 7.62-7.72 (m, 1H),7.4-7.42 (m, 1H), 7.3-7.38 (m, 1H), 5.7-5.8 (m, 1H).

1-(1-Bromo-2,2,2-trifluoroethyl)-2,3-dichlorobenzene (DI24)

1-(2,3-Dichlorophenyl)-2,2,2-trifluoroethanol (DI23) was isolated as apale yellow oil (5.2 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.62-7.64 (d,1H), 7.52-7.54 (m, 1H), 7.29-7.33 (t, 1H), 5.6-5.76 (m, 1H), 2.7 (s,1H); ESIMS m/z 243.9 ([M]⁺). The title compound (DI24) was isolated asan oil (8.7 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.62-7.71 (m, 1H),7.44-7.52 (m, 1H), 7.27-7.3 (s, 1H), 5.81-5.91 (m, 1H).

2-(1-Bromo-2,2,2-trifluoroethyl)-1,4-dichlorobenzene (DI26)

1-(2,5-Dichlorophenyl)-2,2,2-trifluoroethanol (DI25) was isolated as ayellow oil (4.1 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.68-7.7 (s, 1H),7.3-7.37 (m, 2H), 5.51-5.6 (m, 1H), 2.7 (s, 1H); ESIMS m/z 244 ([M]⁺)).The title compound (DI26) was isolated (3.0 g, 60%): ¹H NMR (400 MHz,CDCl₃) δ 7.7-7.78 (m, 1H), 7.3-7.4 (m, 2H), 5.7-5.8 (m, 1H).

1-(1-Bromo-2,2,2-trifluoroethyl)-3,5-bis(trifluoromethyl)benzene (DI28)

1-(3,5-Bis(trifluoromethyl)phenyl)-2,2,2-trifluoroethanol (DI27) wasisolated (3.8 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.98 (m, 3H), 5.25 (m,1H), 3.2 (br, 1H); ESIMS m/z 312.2 ([M]⁺). The title compound (DI28) wasprepared and carried on crude.

1-(1-Bromo-2,2,2-trifluoroethyl)-2,3,5-trichlorobenzene (DI30)

2,2,2-Trifluoro-1-(2,3,5-trichlorophenyl)ethanol (DI29) was isolated asa white solid (4.0 g, 60%): mp 113-115° C.; ¹H NMR (400 MHz, CDCl₃) δ7.62 (d, 1H), 7.50 (d, 1H), 5.60-5.70 (m, 1H), 2.75 (s, 1H); ESIMS m/z278.0 ([M⁺]). The title compound (DI30) was isolated (2.9 g, 60%): ¹HNMR (400 MHz, CDCl₃) δ 7.70 (d, 1H), 7.50 (d, 1H), 5.72-5.82 (m, 1H).

1-(1-Bromo-2,2,2-trifluoroethyl)-3-chloro-5-(trifluoromethyl)benzene(DI32)

1-(3-Chloro-5-(trifluoromethyl)phenyl)-2,2,2-trifluoroethanol (DI31) wasisolated as a pale yellow oil (2.0 g, 50%): ¹H NMR (400 MHz, CDCl₃) δ7.51 (m, 3H), 5.08 (m, 1H), 2.81 (s, 1H); ESIMS m/z 278.1 ([M]⁺). Thetitle compound (DI32) was isolated oil (2.0 g, 40%): ESIMS m/z 342([M]⁺).

5-(1-Bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-methoxybenzene (DI34)

1-(3,5-Dichloro-4-methoxyphenyl)-2,2,2-trifluoroethanol (DI33) wasisolated as an off white solid (0.8 g, 60%); mp 92-95° C.: ¹H NMR (400MHz, CDCl₃) δ 7.41 (s, 2H), 5.00 (m, 1H), 3.89 (s, 3H), 2.64 (m, 1H);ESIMS m/z 274 ([M]⁺). The title compound (DI34) was isolated as acolorless liquid (0.6 g, 57%).

Example 90 Preparation of1-(1-Bromo-2,2,2-trifluoroethyl)-3,5-difluorobenzene (DI36)

The title compound was synthesized in two steps via1-(3,5-difluorophenyl)-2,2,2-trifluoroethanol (DI35, prepared as in Step1, Method A in Example 1; isolated as a colorless oil (0.2 g, 75%): ¹HNMR (400 MHz, CDCl₃) δ 7.05 (m, 2H), 6.88 (m, 1H), 5.06 (m, 1H), 2.66(s, 1H); ESIMS m/z 212 ([M]⁺) and Step 2 in Example 1 and isolated (3.2g, 50%); ¹H NMR (400 MHz, CDCl₃) δ 7.05 (m, 2H), 6.86 (m, 1H), 5.03 (q,J=7.4 Hz, 1H).

The following compounds were made in accordance with the proceduresdisclosed in Example 90.

1-(1-Bromo-2,2,2-trifluoroethyl)-4-chlorobenzene (DI38)

1-(4-Chlorophenyl)-2,2,2-trifluoroethanol (DI37) was isolated as acolorless oil (5.0 g, 99%): ¹H NMR (400 MHz, CDCl₃) δ 7.44-7.38 (m, 4H),5.05 (m, 1H), 2.55 (s, 1H); ESIMS m/z 210 ([M]⁺). The title compound(DI38) was isolated (3.0 g, 46%): ¹H NMR (400 MHz, CDCl₃) δ 7.45 (d,J=8.2 Hz, 2H), 7.37 (d, J=8.2 Hz, 2H), 5.10 (q, J=7.2 Hz, 1H).

1-(1-Bromo-2,2,2-trifluoroethyl)-4-methoxybenzene (DI40)

2,2,2-Trifluoro-1-(4-methoxyphenyl)ethanol (DI39) was isolated as a paleyellow liquid: ¹H NMR (400 MHz, CDCl₃) δ 7.41 (d, J=8.8 Hz, 2H), 6.95(m, J=8.8 Hz, 2H), 5.00 (m, 1H), 3.82 (s, 3H), 2.44 (s, 1H); ESIMS m/z206.1 ([M]⁺). The title compound (DI40) was isolated (3.8 g, 62%).

1-(1-Bromo-2,2,2-trifluoroethyl)-4-fluorobenzene (DI42)

2,2,2-Trifluoro-1-(4-fluorophenyl)ethanol (DI41) was isolated as acolorless oil (5 g, 99%): ¹H NMR (400 MHz, CDCl₃) δ 7.48-7.45 (m, 2H),7.13-7.07 (m, 2H), 5.06 (m, 1H), 2.53 (s, 1H); ESIMS m/z 194 ([M]⁺). Thetitle compound (DI42) was prepared and carried on as crude intermediate.

1-(1-Bromo-2,2,2-trifluoroethyl)-4-methylbenzene (DI44)

2,2,2-Trifluoro-1-(p-tolyl)ethanol (DI43) was isolated as colorless oil(5.0 g, 99%): ¹H NMR (400 MHz, CDCl₃) δ 7.37 (d, J=8.0 Hz, 2H), 7.23 (d,J=8.0 Hz, 2H), 5.02 (m, 1H), 2.46 (m, 1H), 2.37 (s, 3H); ESIMS m/z 190([M]⁺). The title compound (DI44) was isolated (3.0 g, 45%).

1-(1-Bromo-2,2,2-trifluoroethyl)-3-fluorobenzene (DI46)

2,2,2-Trifluoro-1-(3-fluorophenyl)ethanol (DI45) was isolated as acolorless viscous oil (2.8 g, 93%): ¹H NMR (400 MHz, CDCl₃) δ 7.41 (m,1H), 7.25 (m, 2H), 7.14 (m, 1H), 5.06 (m, 1H), 2.60 (s, 1H); ESIMS m/z194 ([M]⁺). The title compound (DI46) was isolated (2.0 g, 61%).

1-(1-Bromo-2,2,2-trifluoroethyl)-2-fluorobenzene (DI48)

2,2,2-Trifluoro-1-(2-fluorophenyl)ethanol (DI47) was isolated as acolorless oil (2.5 g, 99%): ¹H NMR (400 MHz, CDCl₃) δ 7.40 (m, 1H), 7.43(m, 1H), 7.24 (m, 1H), 7.13 (m, 1H), 5.42 (m, 1H), 2.65 (s, 1H); ESIMSm/z 194 ([M]⁺). The title compound (DI48) was isolated (2.0 g, 61%): ¹HNMR (400 MHz, CDCl₃) δ 7.61 (m, 1H), 7.40 (m, 1H), 7.23 (m, 1H), 7.10(m, 1H), 5.40 (m, 1H); GCMS m/z 255 ([M−H]⁻).

Example 91 Preparation of 4-(1H-1,2,4-triazol-1-yl)benzaldehyde (DI5)

To a stirring solution of 4-fluorobenzaldehyde (10.0 g, 80.6 mmol) inDMF (150 mL) were added K₂CO₃ (13.3 g, 96.7 mmol) and 1,2,4-triazole(6.67 g, 96.7 mmol) and the resultant reaction mixture was stirred at120° C. for 6 h. After completion of reaction (by TLC), the reactionmixture was diluted with H₂O and extracted with EtOAc (3×100 mL). Thecombined EtOAc layer was washed with H₂O and brine, dried over Na₂SO₄,and concentrated under reduced pressure to afford the title compound asa solid (9.0 g, 65%): mp 145-149° C.: ¹H NMR (400 MHz, CDCl₃) δ 10.08(s, 1H), 8.70 (s, 1H), 8.16 (s, 1H), 8.06 (d, J=8.0 Hz, 2H), 7.92 (d,J=8.0 Hz, 2H); ESIMS m/z 173.9 ([M+H]⁺).

The following compound was made in accordance with the proceduresdisclosed in Example 91.

5-Formyl-2-(1H-1,2,4-triazol-1-yl)benzonitrile (DI49)

The title compound was isolated (2.8 g, 60%); ¹H NMR (400 MHz, CDCl₃) δ10.10 (s, 1H), 8.98 (s, 1H), 8.35 (s, 1H), 8.30 (d, 1H), 8.22 (s, 1H),8.07 (d, 1H); IR (thin film) 3433, 3120, 1702, 1599, 1510 cm⁻¹.

2-Chloro-4-(1H-1,2,4-triazol-1-yl)benzaldehyde (DI50)

The title compound was isolated as an off white solid (3.0 g, 40%): mp149-151° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.05 (s, 1H), 8.74 (s, 1H), 8.17(s, 1H), 8.10 (s, 1H), 7.90 (m, 2H); ESIMS m/z 208.10 ([M+H]⁺).

5-Methyl-4-(1H-1,2,4-triazol-1-yl)benzaldehyde (DI51)

The title compound was isolated as a white solid (0.5 g, 74%): mp109-111° C.; ¹H NMR (400 MHz, D₆-DMSO) δ 10.06 (s, 1H), 9.00 (s, 1H),8.30 (s, 1H), 7.99 (s, 1H), 7.92 (d, J=9.2 Hz, 1H), 7.69 (d, J=9.2 Hz,1H), 2.30 (s, 3H); ESIMS m/z 188.13 ([M+H]⁺).

Example 92 Preparation of5-Formyl-2-(3-nitro-1H-1,2,4-triazol-1-yl)benzonitrile (DI52)

To a stirring solution of 2-fluoro-5-formylbenzonitrile (0.5 g, 3.3mmol) in DMF (25 mL) were added K₂CO₃ (0.68 g, 4.95 mmol) and3-nitro-1,2,4 triazole (0.45 g, 4.2 mmol) and the resultant reactionmixture was stirred at ambient temperature for 14 h. After completion ofreaction (TLC), the reaction mixture was diluted with water andextracted with EtOAc. The combined EtOAc layer was washed with water andbrine then dried over Na₂SO₄ and concentrated under reduced pressure toafforded the title compound as a pale yellow solid (0.36 g, 45%): mp170-172° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 10.12 (s, 1H), 9.61 (s, 1H),8.69 (s, 1H), 8.45 (d, J=9.3 Hz, 1H), 8.23 (d, J=9.3 Hz, 1H); ESIMS m/z242.3 ([M−H]⁻); IR (thin film) 2238, 1705, 1551, 1314 cm⁻¹.

Example 93 Preparation of 4-(3-Methyl-1H-1,2,4-triazol-1-yl)benzaldehyde(DI53)

To a stirring solution of 4-fluorobenzaldehyde (5.0 g, 40.32 mmol) inDMF (50 mL), were added K₂CO₃ (3.34 g, 40.32 mmol) and3-methyl-1,2,4-trizole (3.34 g, 40.32 mmol) and the resultant reactionmixture was stirred at ambient temperature for 4 h. After completion ofthe reaction (TLC), the reaction mixture was diluted with water andextracted with EtOAc (3×). The combined EtOAc layer was washed withwater and brine then dried over Na₂SO₄ and concentrated under reducedpressure to afforded the title compound as a white solid (4.1 g, 60%):mp 125-128° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.05 (s, 1H), 8.76 (s, 1H),8.02 (d, 2H), 7.85 (d, 2H), 2.50 (s, 3H); ESIMS m/z 188.04 ([M+H]⁺).

The following compound was made in accordance with the proceduresdisclosed in Example 93.

4-(1H-1,2,4-triazol-1-yl)-3-(trifluoromethyl)benzaldehyde (DI54)

The title compound was isolated as white solid (1.05 g, 60%): mp 81-83°C.; ¹H NMR (400 MHz, CDCl₃) δ 10.15 (s, 1H), 8.43 (s, 1H), 8.37 (s, 1H),8.25 (d, J=7.2 Hz, 1H), 8.18 (s, 1H), 7.79 (d, J=7.2 Hz, 1H); ESIMS m/z241.0 ([M]⁺).

4-(3-Nitro-1H-1,2,4-triazol-1-yl)benzaldehyde (DI55)

The title compound was isolated as pale yellow solid (0.10 g, 23%): mp159-161° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.10 (s, 1H), 8.89 (s, 1H), 8.15(m, 2H), 8.00 (m, 2H); ESIMS m/z 217.11 ([M−H]⁻).

3-Bromo-4-(1H-1,2,4-triazol-1-yl)benzaldehyde (DI56)

The title compound was isolated as white solid (3.2 g, 51%): mp 126-128°C.; ¹H NMR (400 MHz, CDCl₃) δ 10.04 (s, 1H), 8.69 (s, 1H), 8.27 (M, 1H,8.18 (s, 1H) 7.99 (d, J=9.2 Hz, 1H), 7.76 (d, J=9.2 Hz, 1H); ESIMS m/z250.9 ([M]⁺).

5-Formyl-2-(3-methyl-1H-1,2,4-triazol-1-yl)benzonitrile (DI57)

The title compound was isolated as white solid (0.13 g, 30%): mp147-149° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.07 (s, 1H), 8.89 (s, 1H), 8.32(d, J=1.8 Hz, 1H), 8.24 (dd, J=8.6, 1.3 Hz, 1H), 8.06 (d, J=8.6 Hz, 1H),2.54 (s, 3H); ESIMS m/z 213.09 ([M+H]⁺); IR (thin film) 2239, 1697 cm⁻¹.

3-Nitro-4-(1H-1,2,4-triazol-1-yl)benzaldehyde (DI58)

The title compound was isolated as pale yellow solid (3.0 g, 60%): mp116-118° C.;

¹H NMR (400 MHz, CDCl₃) δ 10.15 (s, 1H), 8.48 (s, 1H), 8.46 (s, 1H),8.26 (d, J=6.9 Hz, 1H), 8.16 (s, 1H), 7.83 (d, J=6.9 Hz, 1H); ESIMS m/z219.00 ([M+H]⁺).

Example 94 Preparation of 1-(4-Vinylphenyl)-1H-1,2,4-triazole (DI59)

To a stirred solution of 4-[1,2,4]triazol-1-yl-benzaldehyde (9.0 g, 52mmol) in 1,4-dioxane (100 mL), were added K₂CO₃ (10.76 g, 78 mmol) andmethyl triphenyl phosphonium bromide (22.2 g, 62.4 mmol) at roomtemperature. The resultant reaction mixture was heated to 70° C. for 18h. After completion of the reaction (TLC), the reaction mixture wascooled to room temperature and filtered and the obtained filtrate wasconcentrated under reduced pressure. Purification by flashchromatography (SiO₂, 100-200 mesh; 25-30% EtOAc in petroleum ether) toafforded the title compound as a white solid (5.6 g, 63%): ESIMS m/z172.09 ([M+H]⁺).

The following compound was made in accordance with the proceduresdisclosed in Example 94.

1-(2-Methyl-4-vinylphenyl)-1H-1,2,4-triazole (DI60)

The title compound was isolated as an off white solid (1.5 g, 76%): ¹HNMR (400 MHz, CDCl₃) δ 8.25 (s, 1H), 8.11 (s, 1H), 7.35 (m, 2H), 7.27(d, J=8.7 Hz, 1H), 6.74 (m, 1H), 5.82 (d, J=17.3 Hz, 1H), 5.36 (d,J=10.0 Hz, 1H), 2.25 (s, 3H); ESIMS m/z 186.14 ([M+H]⁺).

2-(1H-1,2,4-Triazol-1-yl)-5-vinylbenzonitrile (DI61)

The title compound was isolated as an off-white solid (1.40 g, 71%): mp126-129° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.76 (s, 1H), 8.18 (s, 1H),7.82-7.84 (m, 1H), 7.72-7.80 (m, 2H), 6.70-6.80 (dd, J=17.6, 10.8 Hz,1H), 5.90-5.95 (d, J=17.6 Hz, 1H), 5.50-5.70 (d, J=10.8 Hz, 1H); ESIMSm/z 197.03 ([M+H]⁺).

Example 95 Preparation of2-(3-Nitro-1H-1,2,4-triazol-1-yl)-5-vinylbenzonitrile (DI62)

To a stirred solution of5-formyl-2-(3-nitro-1H-1,2,4-triazol-1-yl)benzonitrile (0.36 g, 1.49mmol) in 1,4-dioxane (25 mL), were added K₂CO₃ (0.3 g, 2.2 mmol) andmethyl triphenyl phosphonium bromide (0.63 g, 1.79 mmol). The resultantreaction mixture was heated to 100° C. for 18 h. After completion of thereaction (TLC), the reaction mixture was cooled to room temperature andfiltered and the obtained filtrate was concentrated under reducedpressure. Purification by flash chromatography (SiO₂, 100-200 mesh;25-30% EtOAc in petroleum ether) to afford the title compound as a solid(0.25 g, 70%): mp 103-105° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 9.50 (s, 1H),8.34 (m, 1H), 7.98 (d, J=7.8 Hz, 1H), 7.68 (d, J=7.8 Hz, 1H), 6.87 (m,1H), 6.20 (d, J=15.7 Hz, 1H), 5.56 (d, J=11.8 Hz, 1H); ESIMS m/z 240.27([M−H]⁻); IR (thin film) 2240, 1514, 1312 cm⁻¹.

The following compound was made in accordance with the proceduresdisclosed in Example 95.

1-(3-Chloro-4-vinylphenyl)-1H-1,2,4-triazole (DI63)

The title compound was isolated as an off-white solid (2.3 g, 80%): mp134-137° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.56 (s, 1H), 8.11 (s, 1H), 7.76(s, 1H), 7.70 (d, J=9.0 Hz, 1H), 7.57 (d, J=9.0 Hz, 1H), 7.10 (m, 1H),5.80 (d, J=17.2 Hz, 1H), 5.47 (d, J=12.4 Hz, 1H); ESIMS m/z 206.04([M+H]⁺.

3-Methyl-1-(4-vinylphenyl)-1H-1,2,4-triazole (DI64)

The title compound was isolated as a white solid (0.6 g, 60%): mp109-111° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.42 (s, 1H), 7.40-7.60 (m, 4H),6.70-7.00 (dd, J=17.6, 10.8 Hz, 1H), 5.80 (d, J=17.6 Hz, 1H), 5.30 (d,J=17.6 Hz, 1H), 2.50 (s, 3H); ESIMS m/z 186.20 ([M+H]⁺).

1-(2-(Trifluoromethyl)-4-vinylphenyl)-1H-1,2,4-triazole (DI65)

The title compound was isolated as a colorless oil (0.6 g, 60%): ¹H NMR(400 MHz, CDCl₃) δ 8.32 (s, 1H), 8.14 (s, 1H), 7.84 (s, 1H), 7.72 (d,J=8.0 Hz, 1H), 7.50 (d, J=7.6 Hz, 1H), 6.70-6.90 (dd, J=17.6, 10.8 Hz,1H), 5.90-6.00 (d, J=17.6 Hz, 1H), 5.50-5.80 (d, J=10.8 Hz 1H); ESIMSm/z 240.16 ([M+H]⁺).

3-Nitro-1-(4-vinylphenyl)-1H-1,2,4-triazole (DI66)

The title compound was isolated as a pale yellow solid (61 mg, 20%): mp137-139° C.;

¹H NMR (400 MHz, CDCl₃) δ 8.60 (s, 1H), 7.68 (d, J=7.7 Hz, 2H), 7.60 (d,J=8.3 Hz, 2H), 6.77 (dd, J=17.7, 10.8, 1H), 5.87 (d, J=17.7 Hz, 1H),5.42 (d, J=10.8 Hz, 1H); ESIMS m/z 217.28 ([M+H]⁺).

1-(2-Bromo-4-vinylphenyl)-1H-1,2,4-triazole (DI67)

The title compound was isolated as a white solid (1.2 g, 40%): mp 75-77°C.; ¹H NMR (400 MHz, CDCl₃) δ 8.48 (s, 1H), 8.12 (s, 1H), 7.75 (s, 1H)7.42 (s, 2H), 6.70 (m, 1H), 5.83 (d, J=18 Hz, 1H), 5.42 (d, J=12 Hz,1H); ESIMS m/z 249.1 ([M]⁺).

2-(3-Methyl-1H-1,2,4-triazol-1-yl)-5-vinylbenzonitrile (DI68)

The title compound was isolated as an off-white solid (0.6 g, 60%): mp96-97° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.66 (s, 1H), 7.80 (s, 1H), 7.74(m, 2H), 6.73 (dd, J=17.6 Hz, 10.8 Hz, 1H), 5.88 (d, J=17.6 Hz, 1H),5.49 (d, J=10.8 Hz, 1H), 2.52 (s, 3H); ESIMS m/z 211.10 ([M+H]⁺); IR(thin film) 2229 cm⁻¹.

1-(2-Nitro-4-vinylphenyl)-1H-1,2,4-triazole (DI69)

The title compound was isolated as a yellow solid (1.78 g, 60%): mp102-104° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.40 (s, 1H), 8.12 (s, 1H), 8.02(s, 1H), 7.72-7.76 (d, J=8.0 Hz, 1H), 7.52-7.56 (d, J=17.6 Hz, 1H),6.70-6.82 (dd, J=17.6, 10.8 Hz, 1H), 5.85-6.00 (d, J=17.6 Hz, 1H),5.50-5.60 (d, J=10.8, Hz 1H); ESIMS m/z 217.0 ([M+H]⁺).

Example 96 Preparation of3-Methyl-2-(1H-1,2,4-triazol-1-yl)-5-vinylbenzonitrile (DI70)

Step 1. 5-Bromo-2-fluoro-3-methylbenzaldehyde

To a stirred solution of di-isopropyl amine (4.01 g, 39.88 mmol) in THF(20 mL) was added n-butyl lithium (1.6 M in hexane) (19.9 mL, 31.91mmol) at −78° C. slowly dropwise over the period of 10 min, the reactionmixture was stirred at −78° C. for 30 min A solution of4-bromo-1-fluoro-2-methylbenzene (5.0 g, 26.6 mmol) in THF (30.0 mL) wasadded at −78° C., and the reaction mixture was stirred for 1 h at thesame temperature. DMF (5.0 mL) was added and stirred at −78° C. foranother 30 min. The reaction was monitored by TLC; then the reactionmixture was quenched with 1N HCl solution (aq) at 0° C. The aqueouslayer was extracted with diethyl ether, washed with water and saturatedbrine solution. The combined organic layer was dried over anhydrousNa₂SO₄ and concentrated under reduced pressure to obtain the crudecompound purified by flash column chromatography (SiO₂, 100-200 mesh;eluting with 5% ethyl acetate/pet ether) to afford the title compound asa white solid (3.6 g, 64%); mp 48-50° C.: ¹H NMR (400 MHz, CDCl₃) δ 8.33(s, 1H), 8.22 (s, 1H), 7.67 (s, 1H), 7.60 (s, 1H), 6.75 (dd, J=17.6,10.8 Hz, 1H), 5.92 (dd, J=17.6, 10.8 Hz, 1H), 5.52 (d, J=17.6 Hz, 1H),2.21 (s, 3H); ESIMS m/z 211.35 ([M−H]⁻).

Step 2. ((E)-5-Bromo-2-fluoro-3-methylbenzaldehyde oxime

To a stirred solution of 5-bromo-2-fluoro-3-methylbenzaldehyde (3.5 g,16.2 mmol) in ethanol (50.0 mL) were added sodium acetate (2.0 g, 24.3mmol) and hydroxylamine hydrochloride (1.69 g, 24.3 mmol) at ambienttemperature. The reaction mixture was stirred at ambient temperature for3 h. The reaction mixture was concentrated on rotavapour to obtain crudecompound, which was washed with water filtered and dried under vacuum toafford the title compound as a white solid: mp 126-127° C.; ¹H NMR (400MHz, CDCl₃) δ 8.32 (s, 1H), 7.73 (d, J=2.4 Hz, 1H), 7.51 (s, 1H), 7.34(d, J=2.4 Hz, 1H), 2.25 (s, 3H); ESIMS m/z 232.10 ([M+H]⁺).

Step 3. 5-Bromo-2-fluoro-3-methylbenzonitrile

A stirred solution of (E)-5-bromo-2-fluoro-3-methylbenzaldehyde oxime(0.5 g, 2.2 mmol) in acetic anhydride (5.0 mL) was heated to reflux for18 h. The reaction mixture was diluted with water and extracted withethyl acetate. The combined ethyl acetate layer was washed with brineand dried over Na₂SO₄ and concentrated under reduced pressure to affordthe crude compound as a light brown gummy material (0.4 g, crude): ESIMSm/z 213.82 ([M+H]⁺).

Step 4. 5-Bromo-3-methyl-2-(1H-1,2,4-triazol-1-yl)benzonitrile (DI71)

To a stirred solution of 5-bromo-2-fluoro-3-methylbenzonitrile (1.0 g,47.716 mmol), in DMF (10.0 mL) was added potassium carbonate (1.95 g,14.14 mmol) followed by 1H-1,2,4-triazole (0.811 g, 9.433 mmol) atambient temperature. The reaction mixture was heated to 140° C. for 18h. The reaction mixture was cooled to ambient temperature, diluted withwater and extracted with ethyl acetate (2×100 mL). The combined ethylacetate layer was washed with brine and dried over Na₂SO₄ andconcentrated under reduced pressure to afford the crude compoundpurified by flash column chromatography (SiO₂, 100-200 mesh; elutingwith 30% ethyl acetate/pet ether) to afford the title compound as a pinksolid (0.6 g, 49%): ¹H NMR (400 MHz, CDCl₃) δ 8.39 (s, 1H), 8.23 (s,1H), 7.91 (d, J=2.4 Hz, 2H), 2.21 (s, 3H), ESIMS m/z 262.57 ([M+H]⁺); IR(thin film) 2231, 554 cm⁻¹.

Step 5. 3-Methyl-2-(1H-1,2,4-triazol-1-yl)-5-vinylbenzonitrile (DI70)

A mixture of 5-bromo-3-methyl-2-(1H-1,2,4-triazol-1-yl)benzonitrile (0.6g, 2.3 mmol), potassium carbonate (0.95 g, 6.87 mmol), vinyl boronicanhydride (0.82 g, 3.43 mmol) and triphenylphosphine (0.13 g, 0.114mmol) in toluene (20.0 mL) were stirred and degassed with argon for 30min. The reaction mixture was heated to reflux for 18 h. The reactionmixture was cooled to ambient temperature, diluted with water andextracted with ethyl acetate (2×100 mL). The combined ethyl acetatelayer was washed with brine, dried over Na₂SO₄ and concentrated underreduced pressure to afford the crude compound that was purified by flashcolumn chromatography (SiO₂, 100-200 mesh; eluting with 30% ethylacetate/pet ether) to afford the title compound as a pink solid (0.25 g,52%): ¹H NMR (400 MHz, CDCl₃) δ 8.33 (s, 1H), 8.22 (s, 1H), 7.67 (s,1H), 7.60 (s, 1H), 6.75 (dd, J=17.6, 10.8 Hz, 1H), 5.92 (d, J=17.6, 1H),5.52 (d, J=10.8 Hz, 1H), 2.21 (s, 3H), ESIMS m/z 211.35 ([M+H]⁺); IR(thin film) 2236, 1511 cm⁻¹.

The following compound was made in accordance with the proceduresdisclosed in Steps 4 and 5 of Example 96.

1-(2-Fluoro-4-vinylphenyl)-1H-1,2,4-triazole (DI72)

1-(4-Bromo-2-fluorophenyl)-1H-1,2,4-triazole (DI73) was isolated as apale yellow solid (3.0 g, 75%): mp 113-116° C.; ¹H NMR (400 MHz, CDCl₃)δ 8.69 (s, 1H), 8.13 (m, 2H), 7.50 (m, 1H), 7.21 (m, 1H); ESIMS m/z241.93 ([M]⁺). The title compound (DI72) was isolated as a yellow solid(1.0 g, 71%): mp 67-70° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.67 (s, 1H), 8.13(s, 1H), 7.94 (m, 1H), 7.41 (m, 1H), 7.24 (s, 1H), 6.75 (dd, J=17.6,10.8 Hz, 1H), 5.81 (d, J=17.6 Hz, 1H), 5.37 (d, J=10.8 Hz, 1H); ESIMSm/z 190.00 ([M+H]⁺).

Example 119 Preparation of1-(1-(4-Vinylphenyl)-1H-1,2,4-triazol-5-yl)ethanone (DI78)

To a stirred solution of 1-(4-vinyl-phenyl)-1H-[1,2,4]triazole (1 g, 5.8mmol) in 25 mL of THF, was added n-BuLi (0.37 g, 5.8 mmol) at −78° C.and stirred for 30 min. To this N-methoxy-N-methyl acetamide in THF(0.66 g, 6.4 mmol) was added and the resultant reaction mixture wasstirred at ambient temperature for 16 h. The reaction mixture wasquenched with a saturated aqueous NH₄Cl solution and extracted withEtOAc (3×50 mL). The combined EtOAc layer was washed with brine anddried over sodium sulphate and concentrated under reduced pressure. Thecrude compound was purified by flash chromatography (SiO₂, 100-200 mesh,40% EtOAc in Pet ether) to afford the title compound as an off whitesolid (280 mg, 23%): mp 97-98° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.10 (s,1H), 7.50 (d, 2H), 7.38 (d, 2H), 6.68 (dd, 1H), 5.85 (d, 1H), 5.38 (d,1H), 2.75 (s, 3H); ESIMS m/z 214.14 ([M+H]⁺).

Example 120 Preparation ofCyclopropyl(1-(4-vinylphenyl)-1H-1,2,4-triazol-5-yl)methanone (DI79)

To a stirred solution of 1-(4-vinyl-phenyl)-1H-[1,2,4]triazole (1 g, 5.8mmol) in 25 mL of THF, was added n-BuLi (0.37 g, 5.8 mmol) at −78° C.and stirred for 30 min. To this N-methoxy N-methylcyclopropoxide in THF(0.82 g, 6.4 mmol) was added and the resultant reaction mixture wasstirred at ambient temperature for 16 h. The reaction mixture wasquenched with a saturated aqueous NH₄Cl solution and extracted withEtOAc (3×25 mL). The combined EtOAc layer was washed with brine anddried over sodium sulphate and concentrated under reduced pressure. Thecrude compound was purified by flash chromatography (SiO₂, 100-200 mesh,40% EtOAc in Pet ether) to afford the title compound as an off whitesolid (420 mg, 30%): mp 90-91° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.12 (s,1H), 7.50 (d, J=7.8 Hz, 2H), 7.38 (d, J=7.8 Hz, 2H), 6.75 (dd, J=16.3,10.7 Hz, 1H), 5.81 (d, J=16.3 Hz, 1H), 5.35 (d, J=10.7 Hz, 1H), 3.22 (m,1H), 1.27 (m, 2H), 1.18 (m, 2H); ESIMS m/z 240.18 ([M+H]⁺); IR (thinfilm) 2922, 1630 cm⁻¹.

Example 121 Preparation of5-(Methylthio)-1-(4-vinylphenyl)-1H-1,2,4-triazole (DI80)

To a stirred solution of 1-(4-vinyl-phenyl)-1H-[1,2,4]triazole (1 g, 5.8mmol) in 50 mL of THF, was added n-BuLi (0.41 g, 6.4 mmol) at −78° C.and stirred for 30 min. To this dimethyldisulfide in THF (0.6 g, 6.43mmol) was added and the resultant reaction mixture was stirred atambient temperature for 16 h. The reaction mixture was quenched with asaturated aqueous NH₄Cl solution and extracted with EtOAc (3×25 mL). Thecombined EtOAc layer was washed with brine and dried over sodiumsulphate and concentrated under reduced pressure. The crude compound waspurified by flash chromatography (SiO₂, 100-200 mesh, 40% EtOAc in Petether) to afford the title compound as an off white solid (0.6 g, 48%):mp 68-70° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.96 (s, 1H), 7.05 (m, 4H), 6.75(dd, J=16.4, 10.7 Hz, 1H), 5.81 (d, J=16.4 Hz, 1H), 5.35 (d, J=10.7 Hz,1H), 2.73 (s, 3H); ESIMS m/z 218.09 ([M+H]⁺).

Example 122 Preparation of 5-Methyl-1-(4-vinylphenyl)-1H-1,2,4-triazole(DI81)

To a stirred solution of 1-(4-vinyl-phenyl)-1H-[1,2,4]triazole (0.5 g,2.9 mmol) in 10 mL of THF, was added n-BuLi (0.22 g, 3.5 mmol) at −78°C. and stirred for 30 min. To this methyl iodide in THF (0.50 g, 3.5mmol) was added and the resultant reaction mixture was stirred atambient temperature for 16 h. The reaction mixture was quenched with asaturated aqueous NH₄Cl solution and extracted with EtOAc (3×25 mL). Thecombined EtOAc layer was washed with brine and dried over sodiumsulphate and concentrated under reduced pressure The crude compound waspurified by flash chromatography (SiO₂, 100-200 mesh, 40% EtOAc in Petether) afford the title compound as a pale brown liquid (250 mg, 46%):¹H NMR (400 MHz, CDCl₃) δ 7.93 (s, 1H), 7.55 (d, J=9 Hz, 2H), 7.42 (d,J=9 Hz, 2H), 6.76 (dd, J=18, 11 Hz, 1H), 5.83 (d, J=18 Hz, 1H), 5.38 (d,J=11 Hz, 1H), 2.55 (s, 3H); ESIMS m/z 186.13 ([M+H]⁺); IR (thin film)1517, 1386, 1182, 847 cm⁻¹.

Example 97 Preparation of(E)-1-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)-1H-1,2,4-triazole(DC1)

To a stirred solution of1-(1-bromo-2,2,2-trifluoro-ethyl)-3,5-dichloro-benzene (2.0 g, 6.51mmol) in 1,2-dichlorobenzene (25 mL), were added1-(4-vinyl-phenyl)-1H-[1,2,4]triazole (2.22 g, 13.0 mmol), CuCl (64 mg,0.65 mmol) and 2,2-bipyridyl (0.2 g, 1.3 mmol). The resultant reactionmixture was degassed with argon for 30 min, then stirred at 180° C. for24 h. After completion of reaction (TLC), the reaction mixture wascooled to ambient temperature and filtered and the filtrate concentratedunder reduced pressure. Purification by flash chromatography (SiO₂,100-200 mesh; 25-30% EtOAc in petroleum ether) afforded the titlecompound as an off-white solid (0.8 g, 32%): mp 93-97° C.; ¹H NMR (300MHz, CDCl₃) δ 8.56 (s, 1H), 8.11 (s, 1H), 7.68 (d, J=8.4 Hz, 2H), 7.54(d, J=8.4 Hz, 2H), 7.38 (t, J=1.8 Hz, 1H), 7.29 (s, 2H), 6.62 (d, J=15.6Hz, 1H), 6.42 (dd, J=15.6, 8.2 Hz, 1H), 4.15 (m, 1H); ESIMS m/z 398.05([M+H]⁺).

Compounds DC2-DC37, DC44, DC45, DC47-49, DC50, DC51, DC54, DC58, DC60,DC62, and DC63-DC67 in Table 1 were made in accordance with theprocedures disclosed in Example 97.

Example 98 Preparation of(E)-2-(3-Nitro-1H-1,2,4-triazol-1-yl)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzonitrile(DC40)

To a stirred solution of2-(3-nitro-1H-1,2,4-triazol-1-yl)-5-vinylbenzonitrile (0.9 g, 3.7 mmol)in 1,2-dichlorobenzene (10 mL), were added5-(1-bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (2.5 g, 7.5mmol), CuCl (73 mg, 0.74 mmol) and 2,2-bipyridyl (0.23 g, 1.49 mmol) andthe resultant reaction mixture was degassed with argon for 30 min andthen stirred at 180° C. for 14 h. After completion of the reaction(TLC), the reaction mixture was cooled to ambient temperature andfiltered and the filtrate was concentrated under reduced pressure.Purification by flash chromatography (SiO₂, 100-200 mesh, 25-30% EtOAcin Pet ether) afforded the title compound as an off white solid (0.9 g,50%): mp 70-73° C.; ¹H NMR (300 MHz, CDCl₃) δ 8.86 (s, 1H), 7.88 (m,3H), 7.44 (s, 2H), 6.67 (d, J=16.0 Hz, 1H), 6.56 (dd, J=16.0, 7.6 Hz,1H), 4.19 (m, 1H); ESIMS m/z 436.11 ([M−2H]⁻).

Example 99 Preparation of(E)-2-(3-Amino-1H-1,2,4-triazol-1-yl)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzonitrile(DC41)

To a stirred solution of(E)-2-(3-nitro-1H-1,2,4-triazol-1-yl)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzonitrile(0.6 g, 1.2 mmol) in MeOH (10 mL), were added Zn dust (0.39 g, 5.98mmol) and sat. aq NH₄Cl solution (5 mL) and the resultant reactionmixture was stirred at ambient temperature for 2 h. After completion ofthe reaction (TLC), the reaction mass was concentrated under reducedpressure. The reaction mass was diluted with CH₂Cl₂, filtered through acelite bed, and the obtained filtrate concentrated under reducedpressure to afford the title compound as a solid (0.5 g, 89%): mp 72-75°C.; ¹H NMR (300 MHz, DMSO-d₆) δ 8.72 (s, 1H), 8.26 (s, 1H), 8.01 (d,J=8.4 Hz, 1H), 7.91 (s, 2H), 7.77 (d, J=8.4 Hz, 1H), 6.42 (dd, J=15.6,9.2 Hz, 1H), 6.83 (d, J=15.6 Hz, 1H), 5.87 (s, 2H), 4.89 (m, 1H); ESIMSm/z 469.95 ([M−H]⁻).

Compound DC38 in Table 1 was made in accordance with the proceduresdisclosed in Example 99. Also, compound DC55 in Table 1 was made fromcompound DC54 in accordance with the procedures disclosed in Example 99,with the exception of using ammonium formate in place of ammoniumchloride.

Example 100 Preparation of(E)-N-(1-(2-Cyano-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)-1H-1,2,4-triazol-3-yl)-N-(cyclopropanecarbonyl)cyclopropanecarboxamide(DC42)

To a stirred solution of(E)-2-(3-amino-1H-1,2,4-triazol-1-yl)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzonitrile(0.1 g, 0.21 mmol) in CH₂Cl₂ at ambient temperature, was addedcyclopropylcarbonyl chloride (0.045 g, 0.42 mmol) and the reactionmixture was stirred for 2 h at ambient temperature. The reaction mixturewas diluted with CH₂Cl₂ and washed with water and brine and dried overNa₂SO₄. Concentration under reduced pressure and purification bypreparative HPLC afforded the title compound as a solid (0.09 g, 79%):mp 104-107° C.; ¹H NMR (300 MHz, CDCl₃) δ 8.78 (s, 2H), 7.83 (s, 1H),7.80 (m, 2H), 7.42 (s, 2H), 6.65 (d, J=16.4 Hz, 1H), 6.51 (dd, J=7.6,8.0 Hz, 1H), 4.17 (m, 1H), 2.16 (m, 2H), 1.25 (m, 4H), 1.00 (m, 4H);ESIMS m/z 609.98 ([M+H]⁺); IR (thin film) 2234, 1714, 1114, 807 cm⁻¹.

Example 101 Preparation of(E)-N-(1-(2-Cyano-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)-1H-1,2,4-triazol-3-yl)cyclopropanecarboxamide(DC43)

To a stirred solution of(E)-2-(3-amino-1H-1,2,4-triazol-1-yl)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzonitrile(0.15 g, 0.31 mmol) in CH₂Cl₂ at 0° C., were added TEA (0.1 g, 1 mmol)and cyclopropylcarbonyl chloride (0.04 g, 0.38 mmol) and the reactionmixture was stirred for 1 h at 0° C. The reaction mixture was dilutedwith CH₂Cl₂ and washed with water and brine and dried over Na₂SO₄.Concentration under reduced pressure and purification by columnchromatography (SiO₂, 100-200 mesh) afforded the title compound as asolid (66 mg, 34%): mp 109-112° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 10.94(br s, 1H), 8.36 (s, 1H), 8.08 (m, J=8.4 Hz, 1H), 7.91 (s, 2H), 7.84 (d,J=8.4 Hz, 1H), 7.13 (dd, J=15.6, 9.2 Hz, 1H), 6.87 (d, J=15.6 Hz, 1H),4.92 (m, 1H), 1.99 (br s, 1H), 0.82 (s, 4H); ESIMS m/z 540.04 ([M+H]⁺);IR (thin film) 3233, 2233, 1699, 1114, 807 cm⁻¹.

Compound DC39 in Table 1 was made in accordance with the proceduresdisclosed in Example 101.

Example 102 Preparation of 1-(4-(1H-1,2,4-triazol-1-yl)phenyl)ethanone(DI74)

To a stirred solution of 4-bromoacetophenone (10 g, 50 mmol) in DMF (100mL), were added 1,2,4-triazole (5 g, 75 mmol), Cs₂CO₃ (32.6 g, 100.5mmol) and CuI (1.4 g, 10.1 mmol) and the resultant reaction mixture wasrefluxed for 48 h. After completion of the reaction (by TLC), thereaction mixture was cooled to ambient temperature and diluted withwater (200 mL) and extracted with EtOAc. The combined organic layer waswashed with brine and dried over Na₂SO₄ and concentrated under reducedpressure. Purification by washing with diethyl ether afforded the titlecompound as a solid (5 g, 96%): ¹H NMR (400 MHz, CDCl₃) δ 8.71 (s, 1H),8.16, (s, 1H), 8.13 (d, J=8.6 Hz, 2H), 7.83 (d, J=8.6 Hz, 2H), 2.66 (s,3H); ESIMS m/z 186.02 ([M−H]⁻).

Example 103 Preparation of1-(4-(1H-1,2,4-triazol-1-yl)phenyl)-3-(3,5-dichlorophenyl)-4,4,4-trifluorobutan-1-one(DI75)

Step 1. 1-(4-(1-(trimethylsilyloxy)vinyl)phenyl)-1H-1,2,4-triazole(DI76)

To a stirred solution of 1-(4-(1H-1,2,4-triazol-1-yl)phenyl)ethanone(4.5 g, 24.0 mmol) in CH₂Cl₂ at 0° C., were added TEA (3.7 g, 36.1 mmol)and trimethylsilyl triflluoromethanesulfonate (8 g, 36 mmol) and theresultant reaction mixture was stirred for 1 h. The reaction mixture wasquenched with a mixture of sat aq sodium bicarbonate solution and ether.The ether layer and was separated, washed with brine, dried over Na₂SO₄and concentrated under reduced pressure to afford the title compound(5.5 g) which was taken directly to next step.

Step 2.1-(4-(1H-1,2,4-triazol-1-yl)phenyl)-3-(3,5-dichlorophenyl)-4,4,4-trifluorobutan-1-one(DI75)

To a stirred solution of1-(4-(1-(trimethylsilyloxy)vinyl)phenyl)-1H-1,2,4-triazole (6 g, 23mmol) and 1-(1-bromo-2,2,2-trifluoro-ethyl)-3,5-dichlorobenzene (7.1 g,34.7 mmol) in 1,2-dichlorobenzene (30 mL) was degassed with argon. Tothis CuCl (0.23 g, 2.31 mmol) and 2,2-bipyridyl (0.73 g, 4.63 mmol) wasadded to the above reaction mixture and the resultant reaction mixturewas heated to 180° C. for 18 h. After completion of the reaction (byTLC), the reaction mixture was absorbed onto silica gel and purified bycolumn chromatography (SiO2; 10% EtOAc in petroleum ether) to affordtitle compound as a solid (3 g, 31%): ¹H NMR (400 MHz, CDCl₃) δ 8.67 (s,1H), 8.15 (s, 1H), 8.10 (d, J=8.3 Hz, 2H), 7.82 (d, J=8.3 Hz, 2H), 7.33(m, 1H), 7.30 (m, 2H), 4.20 (m, 1H), 3.63 (m, 2H); ESIMS m/z 412. 14([M−H]⁻).

Example 104 Preparation of2-(4-(1H-1,2,4-triazol-1-yl)phenyl)-4-(3,5-dichlorophenyl)-5,5,5-trifluoropentan-2-ol(DI77)

To a solution of1-(4-(1H-1,2,4-triazol-1-yl)phenyl)-3-(3,5-dichlorophenyl)-4,4,4-trifluorobutan-1-one(300 mg, 0.726 mmol) in THF cooled to 0° C. was added methylmagnesiumbromide (450 mg, 5 mmol) drop wise. The reaction was stirred for 3 h at0° C., then the reaction mixture was quenched with sat aq NH₄Cl solutionand extracted with ethyl acetate. The combined EtOAc layer was washedwith water and brine, dried over Na₂SO₄ and concentrated under reducedpressure. Purification by column chromatography (SiO₂, 100-200 mesh;20%-25% EtOAc in petroleum ether) afforded the title compound as a solid(100 mg, 32%): ¹H NMR (400 MHz, CDCl₃) δ two diastereoisomers 8.58 (s,1H, minor), 8.48 (s, 1H, major), 8.13 (s, 1H, minor), 8.09 (s, 1H,major), 7.70 (d, J=9.0 Hz, 2H, minor), 7.53 (d, J=9.0 Hz, 2H, minor),7.40 (d, J=9.0 Hz, 2H, major), 7.31 (m, 1H, minor), 7.27 (d, J=9.0 Hz,2H, major), 7.20 (m, 2H, minor), 7.01 (m, 1H, major), 6.75 (m, 2H,major), 350 (m, 1H), 2.50 (m, 2H), 1.56 (s, 3H, major), 1.54 (s, 3H,minor); ESIMS m/z 430.05 ([M+H]⁺).

Example 105 Preparation of(E)-1-(4-(4-(3,5-Dichlorophenyl)-5,5,5-trifluoropent-2-en-2-yl)phenyl)-1H-1,2,4-triazole(DC68)

To a solution of2-(4-(1H-1,2,4-triazol-1-yl)phenyl)-4-(3,5-dichlorophenyl)-5,5,5-trifluoropentan-2-ol(100 mg, 0.233 mmol) in toluene was added a catalytic amount ofp-toluenesulfonic acid (PTSA) and the water was removed by azeotropicdistillation over the course of 12 h. The reaction mixture was cooled toroom temperature and dissolved in ethyl acetate. The solution was washedwith sat aq NaHCO₃ solution and brine, dried over Na₂SO₄ andconcentrated under reduced pressure. Purification by columnchromatography (SiO₂, 100-200 mesh; 20%-25% EtOAc in petroleum ether)afforded the title compound as a solid (30 mg, 31%).

Example 123 Preparation of(E)-5-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(1H-1,2,4-triazol-1-yl)benzaldehyde(DC52)

To a stirred solution of(E)-5-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(1H-1,2,4-triazol-1-yl)benzonitrile(0.3 g, 0.71 mmol) in toluene (10 mL) at −78° C. was added dropwisediisobutylaluminum hydride (DIBAL-H, 1.0 M solution in toluene; 0.85mL), and the reaction mixture was stirred at −78° C. for 20 min. Thereaction mixture was quenched with the addition of 1 N HCl solution,then the aqueous layer was extracted with EtOAc (2×). The combinedorganic layers were washed with brine, dried over Na₂SO₄ andconcentrated under reduced pressure. The crude compound was purified byflash column chromatography (SiO₂; 50% EtOAc/Pet ether) to afford thetitle compound as a yellow oil.

Compound DC53 in Table 1 was made in accordance with the proceduresdisclosed in Example 123.

Example 124 Preparation of(E)-5-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N-methyl-2-(1H-1,2,4-triazol-1-yl)aniline(DC57)

To a stirred solution of(E)-5-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(1H-1,2,4-triazol-1-yl)aniline(0.3 g, 0.7 mmol) in CH₂Cl₂ (10 mL) was added TEA (0.155 mL, 1.09 mmol)and methyl iodide (0.124 g, 0.873 mmol). The reaction was stirred atambient temperature for 18 h. The CH₂Cl₂ layer was washed with water andbrine, dried over Na₂SO₄ and concentrated under reduced pressure. Thecrude compound was purified by flash column chromatography (SiO₂; 50%EtOAc/Pet ether) to afford the title compound as a yellow semi-solid(0.07 g, 70%).

Example 125 Preparation of(E)-5-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(1H-1,2,4-triazol-1-yl)benzoicacid (DC61)

A solution of (E)-ethyl5-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(1H-1,2,4-triazol-1-yl)benzoate(0.2 g, 0.4 mmol) in 6 N HCl (10 mL) was stirred at 100° C. for 18 h.The reaction was cooled to ambient temperature, resulting in a whitesolid precipitate. The precipitate was filtered to afford the titlecompound as a white solid (0.12 g, 60%).

Example 126 Preparation of(Z)-5-((E)-3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N′-hydroxy-2-(1H-1,2,4-triazol-1-yl)benzimidamide(DC59)

A solution of(E)-5-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(1H-1,2,4-triazol-1-yl)benzonitrile(0.3 g, 0.71 mmol), sodium acetate (0.087 g, 1.065 mmol) andhydroxylammonium chloride (0.072 g, 1.065 mmol) in 9:1 ethanol/watermixture (10 mL) was stirred at 70° C. for 8 h. The reaction was cooledto ambient temperature, and the ethanol was evaporated. The residue wasdissolved in water and extracted with EtOAc (2×). The combined organiclayers were washed with brine, dried over Na₂SO₄ and concentrated underreduced pressure to afford the title compound as an off white solid.

Example 127 Preparation of(E)-1-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluoro-3-methoxybut-1-en-1-yl)phenyl)-1H-1,2,4-triazole(DC70)

Step 1.(E)-3-(4-(1H-1,2,4-triazol-1-yl)phenyl)-1-(3,5-dichlorophenyl)prop-2-en-1-one

To a solution of 1-(3,5-dichlorophenyl)ethanone (0.5 g, 2.6 mmol) inethanol (20 mL) was added 4-(1H-1,2,4-triazol-1-yl)benzaldehyde (0.46 g,2.65 mmol) and the reaction was cooled to 0° C. Sodium hydroxide (0.22g, 5.29 mmol) in water (10 mL) was then added and the reaction wasallowed to stir for 2 h at 0° C. The reaction was extracted with EtOAcand the combined organic layers were dried over Na₂SO₄ and concentratedunder reduced pressure to afford the title compound (0.149 g, 17%):);ESIMS m/z 430.05 ([M+H]⁺) 344.08

Step 2.(E)-4-(4-(1H-1,2,4-triazol-1-yl)phenyl)-2-(3,5-dichlorophenyl)-1,1,1-trifluorobut-3-en-2-ol(DC69)

To a solution of(E)-3-(4-(1H-1,2,4-triazol-1-yl)phenyl)-1-(3,5-dichlorophenyl)prop-2-en-1-one(1 g, 3 mmol) in THF (150 mL) was added trifluoromethyltrimethylsilane(0.517 g, 3.644 mmol) and tetra-n-butylammonium fluoride (TBAF) (1.0 M,1 mL) at 0° C. The reaction was slowly warmed to ambient temperature andallowed to stir for 2 h. The reaction was then cooled to 0° C. and 5 MHCl solution was added and the reaction was stirred for an additional 4h at ambient temperature. The reaction was extracted with CH₂Cl₂ and thecombined organic layers were dried over Na₂SO₄ and concentrated underreduced pressure. The crude compound was purified by flash columnchromatography (SiO₂; 25% EtOAc/hexanes) to afford the title compound asan off-white solid (0.3 g, 25%).

Step 3.(E)-1-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluoro-3-methoxybut-1-en-1-yl)phenyl)-1H-1,2,4-triazole(DC70)

To a solution of(E)-4-(4-(1H-1,2,4-triazol-1-yl)phenyl)-2-(3,5-dichlorophenyl)-1,1,1-trifluorobut-3-en-2-ol(0.15 g, 0.36 mmol) in THF (5 mL) was added NaH (60%, 10 mg, 0.44 mmol)at 0° C. The reaction was allowed to stir at 0° C. for 30 min, thenmethyl iodide (61 mg, 0.44 mmol) was added slowly and the reaction waswarmed to ambient temperature and allowed to stir for 4 h. The reactionwas quenched with aq NH₄Cl solution and extracted with CH₂Cl₂. Thecombined organic layers were dried over Na₂SO₄ and concentrated underreduced pressure to afford the title compound as an off-white solid (55mg, 35%).

Prophetic Example F1 Preparation of(E)-2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoyl)-N-ethyl-1-methylhydrazinecarboxamide(F1)

Prophetically,(E)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoicacid can be reacted with N-ethyl-1-methylhydrazinecarboxamide in thepresence of N-(3-dimethylaminopropyl)-N′-ethyl-carbodiimidehydrochloride (EDC.HCl) and DMAP to furnish the title molecule (Org.Lett. 2004, 6, 929-931).

Example 128 Preparation of(E)-2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoyl)-N-(2,2,2-trifluoroethyl)hydrazinecarboxamide(F7)

Step 1. tert-Butyl2-((2,2,2-trifluoroethyl)carbamoyl)hydrazinecarboxylate

To a stirred solution of tert-butyl hydrazinecarboxylate (1.0 g, 8 mmol)in anhydrous benzene (10.0 mL) was added1,1,1-trifluoro-2-isocyanatoethane (1.06 g, 8 mmol) neat via syringe togive a gelatin like mixture. Anhydrous THF was added to give a clearsolution which was stirred for 10 minutes, after which time the reactionmixture was evaporated to afford the title compound as a white solid(1.62 g, 79%): ¹H NMR (400 MHz, CDCl₃) δ 6.63 (s, 1H), 6.40 (d, J=2.2Hz, 1H), 5.84 (s, 1H), 3.88 (qd, J=9.0, 6.6 Hz, 2H), 1.48 (s, 9H); ¹⁹FNMR (376 MHz, CDCl₃) δ −73.20. This material is used without furtherpurification.

Step 2. N-(2,2,2-Trifluoroethyl)hydrazinecarboxamide hydrochloride

To a stirred solution of tert-butyl2-((2,2,2-trifluoroethyl)carbamoyl)hydrazinecarboxylate (1.62 g, 6.30mmol) in anhydrous dioxane (10.0 mL) was added HCl (4M in dioxane, 2-3mL). The reaction mixture was stirred at ambient temperature for 18 h,then heated at reflux for 2-3 h. The reaction mixture was allowed tocool to ambient temperature and then evaporated to afford the titlecompound as a white solid (1.33 g, 109%): ¹H NMR (400 MHz, DMSO-d₆) δ10.12 (s, 3H), 9.25 (s, 1H), 7.72 (t, J=6.5 Hz, 1H), 3.91 (qd, J=9.7,6.5 Hz, 2H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −71.41; ESIMS m/z 156([M−H]⁻). This material is used without further purification.

Step 3.(E)-2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoyl)-N-(2,2,2-trifluoroethyl)hydrazinecarboxamide

To a solution containing(E)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoicacid (120 mg, 0.246 mmol), 1,2-dichloroethane (DCE) (5 mL) was addedsequentially EDC.HCl (70.6 mg, 0.368 mmol),N-(2,2,2-trifluoroethyl)hydrazinecarboxamide hydrochloride (52.3 mg,0.270 mmol) and DMAP (63.0 mg, 0.516 mmol). The reaction mixture wasstirred at ambient temperature for 18 h. The reaction mixture wasdiluted with CH₂Cl₂, washed with 0.1N HCl then with aqueous NaHCO₃,dried (MgSO₄), filtered and evaporated to dryness. The crude product waspurified by flash column chromatography afford the title compound as aglassy oil (40 mg, 26%): ¹H NMR (400 MHz, CDCl₃) δ 8.12 (s, 1H), 7.65(s, 1H), 7.60 (d, J=8.0 Hz, 1H), 7.51 (d, J=6.4 Hz, 1H), 7.40 (s, 3H),6.54 (d, J=15.8 Hz, 1H), 6.42 (dd, J=16.0, 7.7 Hz, 1H), 5.95 (s, 1H),4.10 (s, 1H), 3.91 (m, 2H); ¹⁹F NMR (376 MHz, CDCl₃) δ −68.56, −73.02;ESIMS m/z 627.9 ([M+H]⁺).

Example 129 Preparation of(E)-1-Isopropyl-2-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)benzoyl)-N-(2,2,2-trifluoroethyl)hydrazinecarboxamide(FA3)

DIPEA (0.32 ml, 1.88 mmol),1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium3-oxid hexafluorophosphate (HATU) (263 mg, 0.69 mmol) and1-amino-1-isopropyl-3-(2,2,2-trifluoroethyl)urea hydrochloride (178 mg,0.75 mmol) were added to a stirred solution of2-(trifluoromethyl)-4-[(E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl]benzoicacid (300 mg, 0.63 mmol) in DMF (2 mL) at ambient temperature and thereaction mixture was stirred for 4 h. Water was added to the reactionmixture and it was extracted with EtOAc. The organic layer was washedwith brine followed by water, dried (Na₂SO₄), filtered and concentrated.The residue was purified by column chromatography on silica, elutingwith 20% EtOAc in petroleum ether to afford the title compound as abrown gum (135 mg, 29%).

Example 130 Preparation of1-Isopropyl-N-(2,2,2-trifluoroethyl)hydrazinecarboxamide hydrochloride

Step 1. tert-Butyl2-isopropyl-2-(2,2,2-trifluoroethylcarbamoyl)hydrazine carboxylate

2,2,2-Trifluoroethanamine (284 mg, 2.87 mmol), TEA (0.8 ml, 5.74 mmol))in CH₂Cl₂ (6 mL) were added to the solution of triphosgene (298 mg, 1mmol) in CH₂Cl₂ (8 mL) at −40° C. and the reaction mixture was stirredfor 30 min tert-Butyl N-(isopropylamino)carbamate (JOC, 2013, 78,3541-3552.) (500 mg, 2.87 mmol) in CH₂Cl₂ (4 mL) was then added to thereaction mixture at −40° C. and stirred at ambienttemperature—overnight. Water was added to the reaction mixture and itwas extracted with CH₂Cl₂. The organic layer wad washed with brine,dried (Na₂SO₄), filtered and concentrated to afford the title compoundas an off white solid (580 mg, crude): mp 90-94° C.; ¹H NMR (400 MHz,DMSO-d₆) δ 8.70 (bs, 1H), 6.81 (t, J=6.3, 1H), 3.89-3.80 (m, 2H),3.11-3.08 (m, 1H), 1.40 (s, 9H), 0.97 (d, J=6.0 Hz, 6H); ESIMS m/z 241.9([M-tert-Butyl]⁺).

The following compounds were made in accordance with the proceduresdisclosed in Steps 1 of Example 130.

Benzyl-2-methyl-2-(2,2,2-trifluoroethylcarbamoyl)hydrazinecarboxylate

The title compound was isolated as a colorless gum (8.0 g, 20%): ¹H NMR(300 MHz, DMSO-d₆) δ 9.45 (s, 1H), 7.41 (m, 6H), 5.11 (s, 2H), 3.85-3.73(m, 2H), 2.95 (s, 3H); IR (thin film) 3332, 2960, 1735, 1161, 742 cm⁻¹.

Benzyl 2-((2,2-difluoroethyl)carbamoyl)-2-methylhydrazinecarboxylate

The title compound was isolated as a brown solid: mp 79-82° C.; ¹H NMR(300 MHz, DMSO-d₆) δ 9.39 (bs, 1H), 7.38-7.35 (m, 5H), 6.10-5.75 (m,1H), 5.72 (bs, 1H), 5.10 (s, 2H), 3.41-3.36 (m, 2H), 2.94 (s, 3H).

Benzyl 2-methyl-2-((3,3,3-trifluoropropyl)carbamoyl)hydrazinecarboxylate

The title compound was isolated as a brown solid: ¹H NMR (300 MHz,DMSO-d₆) δ 9.46 (bs, 1H), 7.37-7.30 (m, 5H), 5.10 (s, 2H), 4.50 (bs,1H), 3.31-3.19 (m, 2H), 2.92 (s, 3H), 2.38-2.33 (m, 2H); ESIMS m/z 320.3([M+H]⁺); IR (thin film) 3415, 1647, 1267, 1143, 742, 514 cm⁻¹.

Step 2. 1-Isopropyl-N-(2,2,2-trifluoroethyl)hydrazinecarboxamidehydrochloride

HCl (4 M in dioxane, 10 mL) was added to a stirred solution oftert-butyl N-[isopropyl(2,2,2-trifluoroethylcarbamoyl)amino]carbamate(530 mg, 1.77 mmol) in 1,4-dioxane (5 mL) at 0° C. and the reactionmixture was stirred at ambient temperature for 2 h. The volatiles wereevaporated and the residue was washed with pentane to afford the titlecompound as a pale yellow solid. (360 mg, crude): ¹H NMR (300 MHz,DMSO-d₆) δ 11.2 (bs, 2H), 9.81 (s, 1H), 6.98 (t, J=6.3 Hz, 1H),3.90-3.80 (m, 2H), 3.07-3.03 (m, 1H), 1.18 (d, J=6.6 Hz, 6H); ¹³C NMR(300 MHz, DMSO-d₆) δ 157.06, 126.90, 52.25, 45.33, 17.49; ¹⁹F NMR (300MHz, DMSO-d₆) δ −71.52; ESIMS m/z 200.0 ([M−HCl]⁺).

Example 131 Preparation of1-Methyl-N-(2,2,2-trifluoroethyl)hydrazinecarboxamide hydrochloride

Pd—C (10%, 0.88 g, 8.24 mmol) was added portion wise to a stirredsolution of benzyl N-(2,2,2-trifluoroethylcarbamoylamino)carbamate (8.0g, 27.47 mmol) in MeOH (80 mL) and the reaction mixture was stirred anunder hydrogen atmosphere (30 psi) at ambient temperature for 12 h. Thereaction mixture was filtered through Celite® and washed with MeOH. Thefiltrate was concentrated—and the residue was dissolved in—1,4-dioxane(20 mL) and HCl (4 M in 1,4-dioxane, 10 mL) was added under stirring.After stirring at ambient temperature for 3 h the volatiles wereevaporated under vacuum and the residue was washed with EtOAc. Theprecipitated solid was dried under vacuum to afford the title compoundas a white solid (3 g, 50%): ¹H NMR (300 MHz, DMSO-d₆) δ 9.88 (bs, 2H),7.99 (bs, 1H), 3.94-3.82 (m, 2H), 3.12 (s, 3H); ¹⁹F NMR (300 MHz,DMSO-d₆) δ −71.11; ESIMS m/z 171.2 ([M−HCl]⁺); IR (thin film) 3243,1679, 1565, 1157, 648 cm⁻¹.

The following compounds were made in accordance with the proceduresdisclosed in of Example 131 without subsequent treatment with HCl.

N-(2,2-Difluoroethyl)-1-methylhydrazinecarboxamide

The title compound was isolated as a pale yellow solid: mp 81-84° C.; ¹HNMR (300 MHz, DMSO-d₆) δ 7.00 (t, J=6.3 Hz, 1H), 6.14-5.74 (m, 1H), 4.52(bs, 2H), 3.46-3.32 (m, 2H), 2.95 (s, 3H); EIMS m/z 153.2 ([M]⁺).

1-Methyl-N-(3,3,3-trifluoropropyl)hydrazinecarboxamide

The title compound was isolated as a yellow semi solid: ¹H NMR (300 MHz,DMSO-d₆) δ 6.93 (bs, 1H), 4.40 (bs, 2H), 3.25-3.02 (m, 2H), 2.91 (s,3H), 2.87-2.56 (m, 2H); EIMS m/z 185.2 ([M]⁺); IR (thin film) 3409,1652, 1530, 1144, 763, 552 cm⁻¹.

Example 132 Preparation of 3,5-Dibromo-4-chlorobenzaldehyde

Step 1. Methyl 4-amino-3,5-dibromobenzoate

conc. H₂SO₄ (1.35 mL, 25.48 mmol) was added dropwise to a stirredsolution of 4-amino-3,5-dibromobenzoic acid (5.0 g, 16.99 mmol) in MeOH(50 mL) at ambient temperature and the reaction mixture was then stirredat 80° C. for 8 h. The reaction mixture was allowed to cool to ambienttemperature, volatiles were evaporated and ice-water was added to theresidue and extracted with EtOAc. The organic layer was washed withaqueous NaHCO₃ solution followed by brine and water, dried (Na₂SO₄),filtered and concentrated to afford the title compound as an off whitesolid (5.0 g, 95%): ¹H NMR (300 MHz, DMSO-d₆) δ 7.91 (s, 2H), 6.20 (bs,2H), 3.78 (s, 3H); ESIMS m/z 307.0 ([M]⁺); IR (thin film) 3312, 2953,1726, 595 cm⁻¹.

Step 2. Methyl 3,5-dibromo-4-chlorobenzoate

CuCl₂ (2.82 g, 21.0 mmol) in MeCN (30 mL) was stirred at 80° C. for 30min.—tert-Butylnitrite (2.7 mL, 23 mmol) was then added dropwise at thesame temperature and the mixture was stirred for another 10 min. Methyl4-amino-3,5-dibromobenzoate (5.0 g, 16 mmol) in MeCN (30 mL) was addeddropwise to the reaction mixture and stirred at 80° C. for 30 min. Thereaction mixture was allowed to cool to ambient temperature and aqueousammonia solution (20 mL) was added to the reaction mixture and extractedwith petroleum ether. The organic layer was washed with brine followedby water, dried (Na₂SO₄), filtered and concentrated to afford the titlecompound as an off white solid (4.5 g, 84%). ¹H NMR (300 MHz, DMSO-d₆) δ8.21 (s, 2H), 3.94 (s, 3H); ESIMS m/z 326 ([M]⁺); IR (thin film) 1732,746 cm⁻¹.

Step 3. (3,5-Dibromo-4-chlorophenyl)methanol

NaBH₄ (1.53 g, 40.65 mmol) was added portionwise to a stirred solutionof methyl 3,5-dibromo-4-chlorobenzoate (4.45 g, 13.6 mmol) in MeOH (50mL) at 0° C. The reaction mixture was then stirred at ambienttemperature for 8 h. The volatiles were evaporated and the residue wasdiluted with CH₂Cl₂ and washed with brine followed by water. The organiclayer was dried (Na₂SO₄), filtered and concentrated to afford the titlecompound as an off white solid (3.3 g, 80%): ¹H NMR (300 MHz, DMSO-d₆) δ7.71 (s, 2H), 5.49 (bs, 1H), 4.48 (d, J=4.5 Hz, 2H); ESIMS m/z 297.9([M]⁺); IR (thin film) 3460, 747, 534 cm⁻¹.

Step 4. 3,5-Dibromo-4-chlorobenzaldehyde

Pyridinium chlorochormate (PCC, 3.44 g, 15.9 mmol) was added in oneportion to a stirred solution of (3,5-dibromo-4-chlorophenyl)methanol(3.2 g, 11.0 mmol) in CHCl₃ (40 mL) at ambient temperature and thereaction mixture was stirred—overnight. The reaction mixture wasfiltered through Celite®, the Celite® pad was washed with CHCl₃ and thefiltrate was concentrated to afford the title compound as an off whitesolid (2.0 g, 62%): mp 110-113° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.93 (s,1H), 8.27 (s, 2H); ESIMS m/z 297.0 ([M]⁺).

Example 133 Preparation of 4-Bromo-3,5-dichlorobenzaldehyde

Step 1. Methyl 4-amino-3,5-dichlorobenzoate

conc. H₂SO₄ (2.5 mL, 97.04 mmol) was added drop wise to a stirredsolution of 4-amino-3,5-dichlorobenzoic acid (10.0 g, 48.54 mmol) inMeOH (150 mL) at 0° C. and the reaction mixture was then stirred at 80°C. for 8 h. The volatiles were evaporated; ice-water was added to theresidue and extracted with EtOAc. The combined organic layers werewashed with brine, dried (Na₂SO₄), filtered and concentrated underreduced pressure to afford the title compound as a white solid (7.5 g,70%): ¹H NMR (300 MHz, DMSO-d₆) δ 8.05 (s, 2H), 3.96 (s, 3H); ESIMS m/z282 ([M]⁺); IR (KBr): 1733, 762, 514 cm⁻¹.

Step 2. Methyl 4-bromo-3,5-dichlorobenzoate

CuBr₂ (7.5 g, 34.08 mmol) in MeCN (50 mL) was stirred at 80° C. for 30min.—tert-Butylnitrite (6.5 mL, 54.55 mmol) was added dropwise at thesame temperature and the mixture was stirred for another 10 min. Methyl4-amino-3,5-dichlorobenzoate in MeCN (30 mL) was added dropwise to thereaction mixture at stirred at 80° C. for 30 min. The reaction mixturewas allowed to cool to ambient temperature and aqueous ammonia solution(20 mL) was added and extracted with petroleum ether. The organic layerwas washed with brine followed by water, dried (Na₂SO₄), filtered andconcentrated to afford the title compound as an off white solid (7.5 g,77%): ¹H NMR (300 MHz, DMSO-d₆) δ 8.02 (s, 2H), 3.94 (s, 3H); ESIMS m/z2820M; IR (thin film) 1733, 762, 514 cm⁻¹.

Step 3. (4-Bromo-3,5-dichlorophenyl)methanol

DIBAL-H (1M in toluene, 66 mL, and 66.0 mmol) was added dropwise to astirred solution of methyl 4-bromo-3,5-dichlorobenzoate (7.5 g, 26.0mmol) in THF (50 mL) at −78° C. The reaction mixture was allowed to warmtoward ambient temperature and stirred for 6 h. The reaction mixture waspoured into ice-water and extracted with CH₂Cl₂. The organic layer waswashed with brine followed by water, dried (Na₂SO₄), filtered andconcentrated to afford 6.0 g of a mixture of(4-bromo-3,5-dichlorophenyl)methanol and4-bromo-3,5-dichlorobenzaldehyde—as an off white solid which was takento next step without purification.

Step 4. 4-Bromo-3,5-dichlorobenzaldehyde

PCC (7.5 g, 35.16 mmol) was added in one portion to a stirredsolution—containing a mixture of (4-bromo-3,5-dichlorophenyl)methanoland 4-bromo-3,5-dichlorobenzaldehyde (6.0 g) in CHCl₃ (40 mL) at ambienttemperature and the reaction mixture was stirred overnight. The reactionmixture was filtered through celite. The celite pad was washed withCHCl₃. The filtrate was concentrated to afford the title compound as anoff white solid (3.5 g, 67%): mp 125-128° C.; ¹H NMR (300 MHz, DMSO-d₆)δ 9.96 (s, 1H), 8.10 (s, 2H); ESIMS m/z 252 ([M]⁺).

Example 134 Preparation of(E)-N-(2-Aminoethyl)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamide

Step 1. (E)-tert-Butyl2-(2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamido)ethylcarbamate

PyBOP (420 mg, 0.82 mmol) and DIPEA (0.410 mL, 2.46 mmol) were added toa stirred solution of(E)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoicacid (400 mg, 0.82 mmol) and tert-butyl 2-aminoethylcarbamate (130 mg,0.82 mmol) in CH₂Cl₂ (10 mL) and the reaction mixture was stirred atambient temperature for 18 h. Water was added to the reaction mixturewhich was then extracted with CH₂Cl₂ (25 mL). The organic layer waswashed with 2N HCl followed by a saturated aqueous NaHCO₃ solution andbrine. The organic layer was dried (Na₂SO₄), filtered, concentrated andthe residue was purified by column chromatography on silica (100-200mesh) eluting with 40% EtOAc in petroleum ether to afford the titlecompound as a brown solid (200 mg, 39%): ¹H NMR (400 MHz, DMSO-d₆) δ8.38 (t, J=5.2 Hz, 1H), 7.91-7.89 (m, 3H), 7.58 (d, J=6.8 Hz, 1H), 7.41(d, J=7.6 Hz, 1H), 6.99 (dd, J=15.6, 9.2 Hz, 1H), 6.84 (t, J=6.0 Hz,1H), 6.76 (t, J=15.6 Hz, 1H), 4.84-4.80 (m, 1H), 3.24-3.20 (m, 2H),3.11-3.08 (m, 2H), 1.30 (s, 9H); ESIMS m/z 628.80 ([M+H]⁺); IR (thinfilm) 3365, 1701, 1167, 699, 555 cm⁻¹.

Step 2.(E)-N-(2-Aminoethyl)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamide

TFA (0.5 mL) was added to a stirred solution of (E)-tert-butyl2-(2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamido)ethylcarbamate(200 mg, 0.31 mmol) in CH₂Cl₂ (10 mL) at 0° C. and the reaction mixturewas then stirred at ambient temperature for 18 h. The volatiles wereevaporated under reduced pressure; water was added to the residue andthe mixture was extracted with CH₂Cl₂. The organic layer was washed withbrine, dried (Na₂SO₄), filtered, concentrated and the residue waspurified by column chromatography on silica (100-200 mesh) eluting with1-5% MeOH in CH₂Cl₂ to afford the title compound as a brown solid (50mg, 31%): ¹H NMR (400 MHz, DMSO-d₆) δ 8.56 (bs, 1H), 7.70 (bs, 2H),7.94-7.91 (m, 3H), 7.62-7.59 (m, 1H), 7.50 (d, J=7.6 Hz, 1H), 7.00 (dd,J=15.6, 9.2 Hz, 1H), 6.77 (d, J=15.6 Hz, 1H), 4.84-4.81 (m, 1H),3.46-3.41 (m, 2H), 2.95-2.92 (m, 2H); ESIMS m/z 528.72 ([M+H]⁺); IR(thin film) 3435, 1671, 1113, 722, 555 cm⁻¹.

Example 135 Preparation of(E)-N-(2-Aminoethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(FA10)

To a solution of(E)-N-(2-aminoethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide(0.2 g, 0.385 mmol) in CH₂Cl₂ (4 ml) under a nitrogen atmosphere andcooled in an ice bath was added triphosgene (228 mg, 0.770 mmol) andtriethylamine (0.445 mL, 3.19 mmol). The mixture was stirred at ambienttemperature for 1.5 h, then was treated with 2,2,2-trifluoroethanamine(0.248 mL, 3.01 mmol). After stirring for 18 h at ambient temperature,the mixture was partitioned between water and EtOAc. The aqueous phasewas extracted with EtOAc. The combined organic phases were concentratedin vacuo and the resulting crude oil was purified by columnchromatography on silica eluting with EtOAc and hexanes—to afford thetitle compound as a viscous yellow/green oil (50 mg, 20%).

The following prophetic molecules could be made in accordance with theprocedures disclosed in Prophetic Example F1:

Compound Number Structure F1

F2

F3

F4

F5

F6

F7

F8

F9

F10

F11

F12

F13

F14

F15

F16

F17

F18

F19

F20

F21

F22

F23

F24

F25

F26

F27

F28

F29

F30

F31

F32

F33

F34

F35

F36

F37

F38

F39

F40

The following prophetic molecules could be made in accordance with theprocedures disclosed in this application:

Compound Number R1 R2 R3 R4 R6 R8 R10 R11a X5 R11b F41 F F F H CF₃ H BrCH₃ O CH₂CH₃ F42 F F F H CF₃ H Cl CH₃ O CH₂CH₃ F43 F F F H CF₃ H CF₃ CH₃O CH₂CH₃ F44 F F F H CF₃ H CH₃ CH₃ O CH₂CH₃ F45 F F F H CF₃ H Br CH₃ SCH₂CH₃ F46 F F F H CF₃ H Cl CH₃ S CH₂CH₃ F47 F F F H CF₃ H CF₃ CH₃ SCH₂CH₃ F48 F F F H CF₃ H CH₃ CH₃ S CH₂CH₃ F49 F F F H CF₃ H Br H OCH₂CH₃ F50 F F F H CF₃ H Cl H O CH₂CH₃ F51 F F F H CF₃ H CF₃ H O CH₂CH₃F52 F F F H CF₃ H CH₃ H O CH₂CH₃ F53 F F F H CF₃ H Br H S CH₂CH₃ F54 F FF H CF₃ H Cl H S CH₂CH₃ F55 F F F H CF₃ H CF₃ H S CH₂CH₃ F56 F F F H CF₃H CH₃ H S CH₂CH₃ F57 F F F H CF₃ CF₃ Br H O CH₂CF₃ F58 F F F H CF₃ CF₃Cl H O CH₂CF₃ F59 F F F H CF₃ CF₃ CF₃ H O CH₂CF₃ F60 F F F H CF₃ CF₃ CH₃H O CH₂CF₃ F61 F F F H CF₂CF₃ H Br H O CH₂CF₃ F62 F F F H CF₂CF₃ H Cl HO CH₂CF₃ F63 F F F H CF₂CF₃ H CF₃ H O CH₂CF₃ F64 F F F H CF₂CF₃ H CH₃ HO CH₂CF₃ F65 F F F H CF₃ H Br H O CH₂CF₃ F66 F F F H CF₃ H Cl H O CH₂CF₃F67 F F F H CF₃ H CF₃ H O CH₂CF₃ F68 F F F H CF₃ H CH₃ H O CH₂CF₃ F69 FF F H CF₃ H Br H S CH₂CF₃ F70 F F F H CF₃ H Cl H S CH₂CF₃ F71 F F F HCF₃ H CF₃ H S CH₂CF₃ F72 F F F H CF₃ H CH₃ H S CH₂CF₃ F73 Cl Cl H Cl CF₃H Br CH₃ O CH₂CH₃ F74 Cl Cl H Cl CF₃ H Cl CH₃ O CH₂CH₃ F75 Cl Cl H ClCF₃ H CF₃ CH₃ O CH₂CH₃ F76 Cl Cl H Cl CF₃ H CH₃ CH₃ O CH₂CH₃ F77 Cl Cl HCl CF₃ H Br CH₃ S CH₂CH₃ F78 Cl Cl H Cl CF₃ H Cl CH₃ S CH₂CH₃ F79 Cl ClH Cl CF₃ H CF₃ CH₃ S CH₂CH₃ F80 Cl Cl H Cl CF₃ H CH₃ CH₃ S CH₂CH₃ F81 ClCl H Cl CF₃ H Br H O CH₂CH₃ F82 Cl Cl H Cl CF₃ H Cl H O CH₂CH₃ F83 Cl ClH Cl CF₃ H CF₃ H O CH₂CH₃ F84 Cl Cl H Cl CF₃ H CH₃ H O CH₂CH₃ F85 Cl ClH Cl CF₃ H Br H S CH₂CH₃ F86 Cl Cl H Cl CF₃ H Cl H S CH₂CH₃ F87 Cl Cl HCl CF₃ H CF₃ H S CH₂CH₃ F88 Cl Cl H Cl CF₃ H CH₃ H S CH₂CH₃ F89 Cl Cl HCl CF₃ CF₃ Br H O CH₂CF₃ F90 Cl Cl H Cl CF₃ CF₃ Cl H O CH₂CF₃ F91 Cl ClH Cl CF₃ CF₃ CF₃ H O CH₂CF₃ F92 Cl Cl H Cl CF₃ CF₃ CH₃ H O CH₂CF₃ F93 ClCl H Cl CF₂CF₃ H Br H O CH₂CF₃ F94 Cl Cl H Cl CF₂CF₃ H Cl H O CH₂CF₃ F95Cl Cl H Cl CF₂CF₃ H CF₃ H O CH₂CF₃ F96 Cl Cl H Cl CF₂CF₃ H CH₃ H OCH₂CF₃ F97 Cl Cl H Cl CF₃ H Br H O CH₂CF₃ F98 Cl Cl H Cl CF₃ H Cl H OCH₂CF₃ F99 Cl Cl H Cl CF₃ H CF₃ H O CH₂CF₃ F100 Cl Cl H Cl CF₃ H CH₃ H OCH₂CF₃ F101 Cl Cl H Cl CF₃ H Br H S CH₂CF₃ F102 Cl Cl H Cl CF₃ H Cl H SCH₂CF₃ F103 Cl Cl H Cl CF₃ H CF₃ H S CH₂CF₃ F104 Cl Cl H Cl CF₃ H CH₃ HS CH₂CF₃ F105 H H H OCF₃ CF₃ H Br CH₃ O CH₂CH₃ F106 H H H OCF₃ CF₃ H ClCH₃ O CH₂CH₃ F107 H H H OCF₃ CF₃ H CF₃ CH₃ O CH₂CH₃ F108 H H H OCF₃ CF₃H CH₃ CH₃ O CH₂CH₃ F109 H H H OCF₃ CF₃ H Br CH₃ S CH₂CH₃ F110 H H H OCF₃CF₃ H Cl CH₃ S CH₂CH₃ F111 H H H OCF₃ CF₃ H CF₃ CH₃ S CH₂CH₃ F112 H H HOCF₃ CF₃ H CH₃ CH₃ S CH₂CH₃ F113 H H H OCF₃ CF₃ H Br H O CH₂CH₃ F114 H HH OCF₃ CF₃ H Cl H O CH₂CH₃ F115 H H H OCF₃ CF₃ H CF₃ H O CH₂CH₃ F116 H HH OCF₃ CF₃ H CH₃ H O CH₂CH₃ F117 H H H OCF₃ CF₃ H Br H S CH₂CH₃ F118 H HH OCF₃ CF₃ H Cl H S CH₂CH₃ F119 H H H OCF₃ CF₃ H CF₃ H S CH₂CH₃ F120 H HH OCF₃ CF₃ H CH₃ H S CH₂CH₃ F121 H H H OCF₃ CF₃ CF₃ Br H O CH₂CF₃ F122 HH H OCF₃ CF₃ CF₃ Cl H O CH₂CF₃ F123 H H H OCF₃ CF₃ CF₃ CF₃ H O CH₂CF₃F124 H H H OCF₃ CF₃ CF₃ CH₃ H O CH₂CF₃ F125 H H H OCF₃ CF₂CF₃ H Br H OCH₂CF₃ F126 H H H OCF₃ CF₂CF₃ H Cl H O CH₂CF₃ F127 H H H OCF₃ CF₂CF₃ HCF₃ H O CH₂CF₃ F128 H H H OCF₃ CF₂CF₃ H CH₃ H O CH₂CF₃ F129 H H H OCF₃CF₃ H Br H O CH₂CF₃ F130 H H H OCF₃ CF₃ H Cl H O CH₂CF₃ F131 H H H OCF₃CF₃ H CF₃ H O CH₂CF₃ F132 H H H OCF₃ CF₃ H CH₃ H O CH₂CF₃ F133 H H HOCF₃ CF₃ H Br H S CH₂CF₃ F134 H H H OCF₃ CF₃ H Cl H S CH₂CF₃ F135 H H HOCF₃ CF₃ H CF₃ H S CH₂CF₃ F136 H H H OCF₃ CF₃ H CH₃ H S CH₂CF₃ F137 H FH Br CF₃ H Br CH₃ O CH₂CH₃ F138 H F H Br CF₃ H Cl CH₃ O CH₂CH₃ F139 H FH Br CF₃ H CF₃ CH₃ O CH₂CH₃ F140 H F H Br CF₃ H CH₃ CH₃ O CH₂CH₃ F141 HF H Br CF₃ H Br CH₃ S CH₂CH₃ F142 H F H Br CF₃ H Cl CH₃ S CH₂CH₃ F143 HF H Br CF₃ H CF₃ CH₃ S CH₂CH₃ F144 H F H Br CF₃ H CH₃ CH₃ S CH₂CH₃ F145H F H Br CF₃ H Br H O CH₂CH₃ F146 H F H Br CF₃ H Cl H O CH₂CH₃ F147 H FH Br CF₃ H CF₃ H O CH₂CH₃ F148 H F H Br CF₃ H CH₃ H O CH₂CH₃ F149 H F HBr CF₃ H Br H S CH₂CH₃ F150 H F H Br CF₃ H Cl H S CH₂CH₃ F151 H F H BrCF₃ H CF₃ H S CH₂CH₃ F152 H F H Br CF₃ H CH₃ H S CH₂CH₃ F153 H F H BrCF₃ CF₃ Br H O CH₂CF₃ F154 H F H Br CF₃ CF₃ Cl H O CH₂CF₃ F155 H F H BrCF₃ CF₃ CF₃ H O CH₂CF₃ F156 H F H Br CF₃ CF₃ CH₃ H O CH₂CF₃ F157 H F HBr CF₂CF₃ H Br H O CH₂CF₃ F158 H F H Br CF₂CF₃ H Cl H O CH₂CF₃ F159 H FH Br CF₂CF₃ H CF₃ H O CH₂CF₃ F160 H F H Br CF₂CF₃ H CH₃ H O CH₂CF₃ F161H F H Br CF₃ H Br H O CH₂CF₃ F162 H F H Br CF₃ H Cl H O CH₂CF₃ F163 H FH Br CF₃ H CF₃ H O CH₂CF₃ F164 H F H Br CF₃ H CH₃ H O CH₂CF₃ F165 H F HBr CF₃ H Br H S CH₂CF₃ F166 H F H Br CF₃ H Cl H S CH₂CF₃ F167 H F H BrCF₃ H CF₃ H S CH₂CF₃ F168 H F H Br CF₃ H CH₃ H S CH₂CF₃ F169 H CH₃ Cl HCF₃ H Br CH₃ O CH₂CH₃ F170 H CH₃ Cl H CF₃ H Cl CH₃ O CH₂CH₃ F171 H CH₃Cl H CF₃ H CF₃ CH₃ O CH₂CH₃ F172 H CH₃ Cl H CF₃ H CH₃ CH₃ O CH₂CH₃ F173H CH₃ Cl H CF₃ H Br CH₃ S CH₂CH₃ F174 H CH₃ Cl H CF₃ H Cl CH₃ S CH₂CH₃F175 H CH₃ Cl H CF₃ H CF₃ CH₃ S CH₂CH₃ F176 H CH₃ Cl H CF₃ H CH₃ CH₃ SCH₂CH₃ F177 H CH₃ Cl H CF₃ H Br H O CH₂CH₃ F178 H CH₃ Cl H CF₃ H Cl H OCH₂CH₃ F179 H CH₃ Cl H CF₃ H CF₃ H O CH₂CH₃ F180 H CH₃ Cl H CF₃ H CH₃ HO CH₂CH₃ F181 H CH₃ Cl H CF₃ H Br H S CH₂CH₃ F182 H CH₃ Cl H CF₃ H Cl HS CH₂CH₃ F183 H CH₃ Cl H CF₃ H CF₃ H S CH₂CH₃ F184 H CH₃ Cl H CF₃ H CH₃H S CH₂CH₃ F185 H CH₃ Cl H CF₃ CF₃ Br H O CH₂CF₃ F186 H CH₃ Cl H CF₃ CF₃Cl H O CH₂CF₃ F187 H CH₃ Cl H CF₃ CF₃ CF₃ H O CH₂CF₃ F188 H CH₃ Cl H CF₃CF₃ CH₃ H O CH₂CF₃ F189 H CH₃ Cl H CF₂CF₃ H Br H O CH₂CF₃ F190 H CH₃ ClH CF₂CF₃ H Cl H O CH₂CF₃ F191 H CH₃ Cl H CF₂CF₃ H CF₃ H O CH₂CF₃ F192 HCH₃ Cl H CF₂CF₃ H CH₃ H O CH₂CF₃ F193 H CH₃ Cl H CF₃ H Br H O CH₂CF₃F194 H CH₃ Cl H CF₃ H Cl H O CH₂CF₃ F195 H CH₃ Cl H CF₃ H CF₃ H O CH₂CF₃F196 H CH₃ Cl H CF₃ H CH₃ H O CH₂CF₃ F197 H CH₃ Cl H CF₃ H Br H S CH₂CF₃F198 H CH₃ Cl H CF₃ H Cl H S CH₂CF₃ F199 H CH₃ Cl H CF₃ H CF₃ H S CH₂CF₃F200 H CH₃ Cl H CF₃ H CH₃ H S CH₂CF₃ F201 H Cl CH₃ H CF₃ H Br CH₃ OCH₂CH₃ F202 H Cl CH₃ H CF₃ H Cl CH₃ O CH₂CH₃ F203 H Cl CH₃ H CF₃ H CF₃CH₃ O CH₂CH₃ F204 H Cl CH₃ H CF₃ H CH₃ CH₃ O CH₂CH₃ F205 H Cl CH₃ H CF₃H Br CH₃ S CH₂CH₃ F206 H Cl CH₃ H CF₃ H Cl CH₃ S CH₂CH₃ F207 H Cl CH₃ HCF₃ H CF₃ CH₃ S CH₂CH₃ F208 H Cl CH₃ H CF₃ H CH₃ CH₃ S CH₂CH₃ F209 H ClCH₃ H CF₃ H Br H O CH₂CH₃ F210 H Cl CH₃ H CF₃ H Cl H O CH₂CH₃ F211 H ClCH₃ H CF₃ H CF₃ H O CH₂CH₃ F212 H Cl CH₃ H CF₃ H CH₃ H O CH₂CH₃ F213 HCl CH₃ H CF₃ H Br H S CH₂CH₃ F214 H Cl CH₃ H CF₃ H Cl H S CH₂CH₃ F215 HCl CH₃ H CF₃ H CF₃ H S CH₂CH₃ F216 H Cl CH₃ H CF₃ H CH₃ H S CH₂CH₃ F217H Cl CH₃ H CF₃ CF₃ Br H O CH₂CF₃ F218 H Cl CH₃ H CF₃ CF₃ Cl H O CH₂CF₃F219 H Cl CH₃ H CF₃ CF₃ CF₃ H O CH₂CF₃ F220 H Cl CH₃ H CF₃ CF₃ CH₃ H OCH₂CF₃ F221 H Cl CH₃ H CF₂CF₃ H Br H O CH₂CF₃ F222 H Cl CH₃ H CF₂CF₃ HCl H O CH₂CF₃ F223 H Cl CH₃ H CF₂CF₃ H CF₃ H O CH₂CF₃ F224 H Cl CH₃ HCF₂CF₃ H CH₃ H O CH₂CF₃ F225 H Cl CH₃ H CF₃ H Br H O CH₂CF₃ F226 H ClCH₃ H CF₃ H Cl H O CH₂CF₃ F227 H Cl CH₃ H CF₃ H CF₃ H O CH₂CF₃ F228 H ClCH₃ H CF₃ H CH₃ H O CH₂CF₃ F229 H Cl CH₃ H CF₃ H Br H S CH₂CF₃ F230 H ClCH₃ H CF₃ H Cl H S CH₂CF₃ F231 H Cl CH₃ H CF₃ H CF₃ H S CH₂CF₃ F232 H ClCH₃ H CF₃ H CH₃ H S CH₂CF₃ F233 H CH₃ F CH₃ CF₃ H Br CH₃ O CH₂CH₃ F234 HCH₃ F CH₃ CF₃ H Cl CH₃ O CH₂CH₃ F235 H CH₃ F CH₃ CF₃ H CF₃ CH₃ O CH₂CH₃F236 H CH₃ F CH₃ CF₃ H CH₃ CH₃ O CH₂CH₃ F237 H CH₃ F CH₃ CF₃ H Br CH₃ SCH₂CH₃ F238 H CH₃ F CH₃ CF₃ H Cl CH₃ S CH₂CH₃ F239 H CH₃ F CH₃ CF₃ H CF₃CH₃ S CH₂CH₃ F240 H CH₃ F CH₃ CF₃ H CH₃ CH₃ S CH₂CH₃ F241 H CH₃ F CH₃CF₃ H Br H O CH₂CH₃ F242 H CH₃ F CH₃ CF₃ H Cl H O CH₂CH₃ F243 H CH₃ FCH₃ CF₃ H CF₃ H O CH₂CH₃ F244 H CH₃ F CH₃ CF₃ H CH₃ H O CH₂CH₃ F245 HCH₃ F CH₃ CF₃ H Br H S CH₂CH₃ F246 H CH₃ F CH₃ CF₃ H Cl H S CH₂CH₃ F247H CH₃ F CH₃ CF₃ H CF₃ H S CH₂CH₃ F248 H CH₃ F CH₃ CF₃ H CH₃ H S CH₂CH₃F249 H CH₃ F CH₃ CF₃ CF₃ Br H O CH₂CF₃ F250 H CH₃ F CH₃ CF₃ CF₃ Cl H OCH₂CF₃ F251 H CH₃ F CH₃ CF₃ CF₃ CF₃ H O CH₂CF₃ F252 H CH₃ F CH₃ CF₃ CF₃CH₃ H O CH₂CF₃ F253 H CH₃ F CH₃ CF₂CF₃ H Br H O CH₂CF₃ F254 H CH₃ F CH₃CF₂CF₃ H Cl H O CH₂CF₃ F255 H CH₃ F CH₃ CF₂CF₃ H CF₃ H O CH₂CF₃ F256 HCH₃ F CH₃ CF₂CF₃ H CH₃ H O CH₂CF₃ F257 H CH₃ F CH₃ CF₃ H Br H O CH₂CF₃F258 H CH₃ F CH₃ CF₃ H Cl H O CH₂CF₃ F259 H CH₃ F CH₃ CF₃ H CF₃ H OCH₂CF₃ F260 H CH₃ F CH₃ CF₃ H CH₃ H O CH₂CF₃ F261 H CH₃ F CH₃ CF₃ H Br HS CH₂CF₃ F262 H CH₃ F CH₃ CF₃ H Cl H S CH₂CF₃ F263 H CH₃ F CH₃ CF₃ H CF₃H S CH₂CF₃ F264 H CH₃ F CH₃ CF₃ H CH₃ H S CH₂CF₃ F265 H Cl H Br CF₃ H BrCH₃ O CH₂CH₃ F266 H Cl H Br CF₃ H Cl CH₃ O CH₂CH₃ F267 H Cl H Br CF₃ HCF₃ CH₃ O CH₂CH₃ F268 H Cl H Br CF₃ H CH₃ CH₃ O CH₂CH₃ F269 H Cl H BrCF₃ H Br CH₃ S CH₂CH₃ F270 H Cl H Br CF₃ H Cl CH₃ S CH₂CH₃ F271 H Cl HBr CF₃ H CF₃ CH₃ S CH₂CH₃ F272 H Cl H Br CF₃ H CH₃ CH₃ S CH₂CH₃ F273 HCl H Br CF₃ H Br H O CH₂CH₃ F274 H Cl H Br CF₃ H Cl H O CH₂CH₃ F275 H ClH Br CF₃ H CF₃ H O CH₂CH₃ F276 H Cl H Br CF₃ H CH₃ H O CH₂CH₃ F277 H ClH Br CF₃ H Br H S CH₂CH₃ F278 H Cl H Br CF₃ H Cl H S CH₂CH₃ F279 H Cl HBr CF₃ H CF₃ H S CH₂CH₃ F280 H Cl H Br CF₃ H CH₃ H S CH₂CH₃ F281 H Cl HBr CF₃ CF₃ Br H O CH₂CF₃ F282 H Cl H Br CF₃ CF₃ Cl H O CH₂CF₃ F283 H ClH Br CF₃ CF₃ CF₃ H O CH₂CF₃ F284 H Cl H Br CF₃ CF₃ CH₃ H O CH₂CF₃ F285 HCl H Br CF₂CF₃ H Br H O CH₂CF₃ F286 H Cl H Br CF₂CF₃ H Cl H O CH₂CF₃F287 H Cl H Br CF₂CF₃ H CF₃ H O CH₂CF₃ F288 H Cl H Br CF₂CF₃ H CH₃ H OCH₂CF₃ F289 H Cl H Br CF₃ H Br H O CH₂CF₃ F290 H Cl H Br CF₃ H Cl H OCH₂CF₃ F291 H Cl H Br CF₃ H CF₃ H O CH₂CF₃ F292 H Cl H Br CF₃ H CH₃ H OCH₂CF₃ F293 H Cl H Br CF₃ H Br H S CH₂CF₃ F294 H Cl H Br CF₃ H Cl H SCH₂CF₃ F295 H Cl H Br CF₃ H CF₃ H S CH₂CF₃ F296 H Cl H Br CF₃ H CH₃ H SCH₂CF₃ F297 H H Br Br CF₃ H Br CH₃ O CH₂CH₃ F298 H H Br Br CF₃ H Cl CH₃O CH₂CH₃ F299 H H Br Br CF₃ H CF₃ CH₃ O CH₂CH₃ F300 H H Br Br CF₃ H CH₃CH₃ O CH₂CH₃ F301 H H Br Br CF₃ H Br CH₃ S CH₂CH₃ F302 H H Br Br CF₃ HCl CH₃ S CH₂CH₃ F303 H H Br Br CF₃ H CF₃ CH₃ S CH₂CH₃ F304 H H Br Br CF₃H CH₃ CH₃ S CH₂CH₃ F305 H H Br Br CF₃ H Br H O CH₂CH₃ F306 H H Br Br CF₃H Cl H O CH₂CH₃ F307 H H Br Br CF₃ H CF₃ H O CH₂CH₃ F308 H H Br Br CF₃ HCH₃ H O CH₂CH₃ F309 H H Br Br CF₃ H Br H S CH₂CH₃ F310 H H Br Br CF₃ HCl H S CH₂CH₃ F311 H H Br Br CF₃ H CF₃ H S CH₂CH₃ F312 H H Br Br CF₃ HCH₃ H S CH₂CH₃ F313 H H Br Br CF₃ CF₃ Br H O CH₂CF₃ F314 H H Br Br CF₃CF₃ Cl H O CH₂CF₃ F315 H H Br Br CF₃ CF₃ CF₃ H O CH₂CF₃ F316 H H Br BrCF₃ CF₃ CH₃ H O CH₂CF₃ F317 H H Br Br CF₂CF₃ H Br H O CH₂CF₃ F318 H H BrBr CF₂CF₃ H Cl H O CH₂CF₃ F319 H H Br Br CF₂CF₃ H CF₃ H O CH₂CF₃ F320 HH Br Br CF₂CF₃ H CH₃ H O CH₂CF₃ F321 H H Br Br CF₃ H Br H O CH₂CF₃ F322H H Br Br CF₃ H Cl H O CH₂CF₃ F323 H H Br Br CF₃ H CF₃ H O CH₂CF₃ F324 HH Br Br CF₃ H CH₃ H O CH₂CF₃ F325 H H Br Br CF₃ H Br H S CH₂CF₃ F326 H HBr Br CF₃ H Cl H S CH₂CF₃ F327 H H Br Br CF₃ H CF₃ H S CH₂CF₃ F328 H HBr Br CF₃ H CH₃ H S CH₂CF₃ F329 H H Cl NO₂ CF₃ H Br CH₃ O CH₂CH₃ F330 HH Cl NO₂ CF₃ H Cl CH₃ O CH₂CH₃ F331 H H Cl NO₂ CF₃ H CF₃ CH₃ O CH₂CH₃F332 H H Cl NO₂ CF₃ H CH₃ CH₃ O CH₂CH₃ F333 H H Cl NO₂ CF₃ H Br CH₃ SCH₂CH₃ F334 H H Cl NO₂ CF₃ H Cl CH₃ S CH₂CH₃ F335 H H Cl NO₂ CF₃ H CF₃CH₃ S CH₂CH₃ F336 H H Cl NO₂ CF₃ H CH₃ CH₃ S CH₂CH₃ F337 H H Cl NO₂ CF₃H Br H O CH₂CH₃ F338 H H Cl NO₂ CF₃ H Cl H O CH₂CH₃ F339 H H Cl NO₂ CF₃H CF₃ H O CH₂CH₃ F340 H H Cl NO₂ CF₃ H CH₃ H O CH₂CH₃ F341 H H Cl NO₂CF₃ H Br H S CH₂CH₃ F342 H H Cl NO₂ CF₃ H Cl H S CH₂CH₃ F343 H H Cl NO₂CF₃ H CF₃ H S CH₂CH₃ F344 H H Cl NO₂ CF₃ H CH₃ H S CH₂CH₃ F345 H H ClNO₂ CF₃ CF₃ Br H O CH₂CF₃ F346 H H Cl NO₂ CF₃ CF₃ Cl H O CH₂CF₃ F347 H HCl NO₂ CF₃ CF₃ CF₃ H O CH₂CF₃ F348 H H Cl NO₂ CF₃ CF₃ CH₃ H O CH₂CF₃F349 H H Cl NO₂ CF₂CF₃ H Br H O CH₂CF₃ F350 H H Cl NO₂ CF₂CF₃ H Cl H OCH₂CF₃ F351 H H Cl NO₂ CF₂CF₃ H CF₃ H O CH₂CF₃ F352 H H Cl NO₂ CF₂CF₃ HCH₃ H O CH₂CF₃ F353 H H Cl NO₂ CF₃ H Br H O CH₂CF₃ F354 H H Cl NO₂ CF₃ HCl H O CH₂CF₃ F355 H H Cl NO₂ CF₃ H CF₃ H O CH₂CF₃ F356 H H Cl NO₂ CF₃ HCH₃ H O CH₂CF₃ F357 H H Cl NO₂ CF₃ H Br H S CH₂CF₃ F358 H H Cl NO₂ CF₃ HCl H S CH₂CF₃ F359 H H Cl NO₂ CF₃ H CF₃ H S CH₂CF₃ F360 H H Cl NO₂ CF₃ HCH₃ H S CH₂CF₃ F361 H H F CN CF₃ H Br CH₃ O CH₂CH₃ F362 H H F CN CF₃ HCl CH₃ O CH₂CH₃ F363 H H F CN CF₃ H CF₃ CH₃ O CH₂CH₃ F364 H H F CN CF₃ HCH₃ CH₃ O CH₂CH₃ F365 H H F CN CF₃ H Br CH₃ S CH₂CH₃ F366 H H F CN CF₃ HCl CH₃ S CH₂CH₃ F367 H H F CN CF₃ H CF₃ CH₃ S CH₂CH₃ F368 H H F CN CF₃ HCH₃ CH₃ S CH₂CH₃ F369 H H F CN CF₃ H Br H O CH₂CH₃ F370 H H F CN CF₃ HCl H O CH₂CH₃ F371 H H F CN CF₃ H CF₃ H O CH₂CH₃ F372 H H F CN CF₃ H CH₃H O CH₂CH₃ F373 H H F CN CF₃ H Br H S CH₂CH₃ F374 H H F CN CF₃ H Cl H SCH₂CH₃ F375 H H F CN CF₃ H CF₃ H S CH₂CH₃ F376 H H F CN CF₃ H CH₃ H SCH₂CH₃ F377 H H F CN CF₃ CF₃ Br H O CH₂CF₃ F378 H H F CN CF₃ CF₃ Cl H OCH₂CF₃ F379 H H F CN CF₃ CF₃ CF₃ H O CH₂CF₃ F380 H H F CN CF₃ CF₃ CH₃ HO CH₂CF₃ F381 H H F CN CF₂CF₃ H Br H O CH₂CF₃ F382 H H F CN CF₂CF₃ H ClH O CH₂CF₃ F383 H H F CN CF₂CF₃ H CF₃ H O CH₂CF₃ F384 H H F CN CF₂CF₃ HCH₃ H O CH₂CF₃ F385 H H F CN CF₃ H Br H O CH₂CF₃ F386 H H F CN CF₃ H ClH O CH₂CF₃ F387 H H F CN CF₃ H CF₃ H O CH₂CF₃ F388 H H F CN CF₃ H CH₃ HO CH₂CF₃ F389 H H F CN CF₃ H Br H S CH₂CF₃ F390 H H F CN CF₃ H Cl H SCH₂CF₃ F391 H H F CN CF₃ H CF₃ H S CH₂CF₃ F392 H H F CN CF₃ H CH₃ H SCH₂CF₃ F393 H Cl OCF₃ Cl CF₃ H Br CH₃ O CH₂CH₃ F394 H Cl OCF₃ Cl CF₃ HCl CH₃ O CH₂CH₃ F395 H Cl OCF₃ Cl CF₃ H CF₃ CH₃ O CH₂CH₃ F396 H Cl OCF₃Cl CF₃ H CH₃ CH₃ O CH₂CH₃ F397 H Cl OCF₃ Cl CF₃ H Br CH₃ S CH₂CH₃ F398 HCl OCF₃ Cl CF₃ H Cl CH₃ S CH₂CH₃ F399 H Cl OCF₃ Cl CF₃ H CF₃ CH₃ SCH₂CH₃ F400 H Cl OCF₃ Cl CF₃ H CH₃ CH₃ S CH₂CH₃ F401 H Cl OCF₃ Cl CF₃ HBr H O CH₂CH₃ F402 H Cl OCF₃ Cl CF₃ H Cl H O CH₂CH₃ F403 H Cl OCF₃ ClCF₃ H CF₃ H O CH₂CH₃ F404 H Cl OCF₃ Cl CF₃ H CH₃ H O CH₂CH₃ F405 H ClOCF₃ Cl CF₃ H Br H S CH₂CH₃ F406 H Cl OCF₃ Cl CF₃ H Cl H S CH₂CH₃ F407 HCl OCF₃ Cl CF₃ H CF₃ H S CH₂CH₃ F408 H Cl OCF₃ Cl CF₃ H CH₃ H S CH₂CH₃F409 H Cl OCF₃ Cl CF₃ CF₃ Br H O CH₂CF₃ F410 H Cl OCF₃ Cl CF₃ CF₃ Cl H OCH₂CF₃ F411 H Cl OCF₃ Cl CF₃ CF₃ CF₃ H O CH₂CF₃ F412 H Cl OCF₃ Cl CF₃CF₃ CH₃ H O CH₂CF₃ F413 H Cl OCF₃ Cl CF₂CF₃ H Br H O CH₂CF₃ F414 H ClOCF₃ Cl CF₂CF₃ H Cl H O CH₂CF₃ F415 H Cl OCF₃ Cl CF₂CF₃ H CF₃ H O CH₂CF₃F416 H Cl OCF₃ Cl CF₂CF₃ H CH₃ H O CH₂CF₃ F417 H Cl OCF₃ Cl CF₃ H Br H OCH₂CF₃ F418 H Cl OCF₃ Cl CF₃ H Cl H O CH₂CF₃ F419 H Cl OCF₃ Cl CF₃ H CF₃H O CH₂CF₃ F420 H Cl OCF₃ Cl CF₃ H CH₃ H O CH₂CF₃ F421 H Cl OCF₃ Cl CF₃H Br H S CH₂CF₃ F422 H Cl OCF₃ Cl CF₃ H Cl H S CH₂CF₃ F423 H Cl OCF₃ ClCF₃ H CF₃ H S CH₂CF₃ F424 H Cl OCF₃ Cl CF₃ H CH₃ H S CH₂CF₃ F425 H Cl CNCl CF₃ H Br CH₃ O CH₂CH₃ F426 H Cl CN Cl CF₃ H Cl CH₃ O CH₂CH₃ F427 H ClCN Cl CF₃ H CF₃ CH₃ O CH₂CH₃ F428 H Cl CN Cl CF₃ H CH₃ CH₃ O CH₂CH₃ F429H Cl CN Cl CF₃ H Br CH₃ S CH₂CH₃ F430 H Cl CN Cl CF₃ H Cl CH₃ S CH₂CH₃F431 H Cl CN Cl CF₃ H CF₃ CH₃ S CH₂CH₃ F432 H Cl CN Cl CF₃ H CH₃ CH₃ SCH₂CH₃ F433 H Cl CN Cl CF₃ H Br H O CH₂CH₃ F434 H Cl CN Cl CF₃ H Cl H OCH₂CH₃ F435 H Cl CN Cl CF₃ H CF₃ H O CH₂CH₃ F436 H Cl CN Cl CF₃ H CH₃ HO CH₂CH₃ F437 H Cl CN Cl CF₃ H Br H S CH₂CH₃ F438 H Cl CN Cl CF₃ H Cl HS CH₂CH₃ F439 H Cl CN Cl CF₃ H CF₃ H S CH₂CH₃ F440 H Cl CN Cl CF₃ H CH₃H S CH₂CH₃ F441 H Cl CN Cl CF₃ CF₃ Br H O CH₂CF₃ F442 H Cl CN Cl CF₃ CF₃Cl H O CH₂CF₃ F443 H Cl CN Cl CF₃ CF₃ CF₃ H O CH₂CF₃ F444 H Cl CN Cl CF₃CF₃ CH₃ H O CH₂CF₃ F445 H Cl CN Cl CF₂CF₃ H Br H O CH₂CF₃ F446 H Cl CNCl CF₂CF₃ H Cl H O CH₂CF₃ F447 H Cl CN Cl CF₂CF₃ H CF₃ H O CH₂CF₃ F448 HCl CN Cl CF₂CF₃ H CH₃ H O CH₂CF₃ F449 H Cl CN Cl CF₃ H Br H O CH₂CF₃F450 H Cl CN Cl CF₃ H Cl H O CH₂CF₃ F451 H Cl CN Cl CF₃ H CF₃ H O CH₂CF₃F452 H Cl CN Cl CF₃ H CH₃ H O CH₂CF₃ F453 H Cl CN Cl CF₃ H Br H S CH₂CF₃F454 H Cl CN Cl CF₃ H Cl H S CH₂CF₃ F455 H Cl CN Cl CF₃ H CF₃ H S CH₂CF₃F456 H Cl CN Cl CF₃ H CH₃ H S CH₂CF₃ F457 H CH₃ H Br CF₃ H Br CH₃ OCH₂CH₃ F458 H CH₃ H Br CF₃ H Cl CH₃ O CH₂CH₃ F459 H CH₃ H Br CF₃ H CF₃CH₃ O CH₂CH₃ F460 H CH₃ H Br CF₃ H CH₃ CH₃ O CH₂CH₃ F461 H CH₃ H Br CF₃H Br CH₃ S CH₂CH₃ F462 H CH₃ H Br CF₃ H Cl CH₃ S CH₂CH₃ F463 H CH₃ H BrCF₃ H CF₃ CH₃ S CH₂CH₃ F464 H CH₃ H Br CF₃ H CH₃ CH₃ S CH₂CH₃ F465 H CH₃H Br CF₃ H Br H O CH₂CH₃ F466 H CH₃ H Br CF₃ H Cl H O CH₂CH₃ F467 H CH₃H Br CF₃ H CF₃ H O CH₂CH₃ F468 H CH₃ H Br CF₃ H CH₃ H O CH₂CH₃ F469 HCH₃ H Br CF₃ H Br H S CH₂CH₃ F470 H CH₃ H Br CF₃ H Cl H S CH₂CH₃ F471 HCH₃ H Br CF₃ H CF₃ H S CH₂CH₃ F472 H CH₃ H Br CF₃ H CH₃ H S CH₂CH₃ F473H CH₃ H Br CF₃ CF₃ Br H O CH₂CF₃ F474 H CH₃ H Br CF₃ CF₃ Cl H O CH₂CF₃F475 H CH₃ H Br CF₃ CF₃ CF₃ H O CH₂CF₃ F476 H CH₃ H Br CF₃ CF₃ CH₃ H OCH₂CF₃ F477 H CH₃ H Br CF₂CF₃ H Br H O CH₂CF₃ F478 H CH₃ H Br CF₂CF₃ HCl H O CH₂CF₃ F479 H CH₃ H Br CF₂CF₃ H CF₃ H O CH₂CF₃ F480 H CH₃ H BrCF₂CF₃ H CH₃ H O CH₂CF₃ F481 H CH₃ H Br CF₃ H Br H O CH₂CF₃ F482 H CH₃ HBr CF₃ H Cl H O CH₂CF₃ F483 H CH₃ H Br CF₃ H CF₃ H O CH₂CF₃ F484 H CH₃ HBr CF₃ H CH₃ H O CH₂CF₃ F485 H CH₃ H Br CF₃ H Br H S CH₂CF₃ F486 H CH₃ HBr CF₃ H Cl H S CH₂CF₃ F487 H CH₃ H Br CF₃ H CF₃ H S CH₂CF₃ F488 H CH₃ HBr CF₃ H CH₃ H S CH₂CF₃ F489 H H F CH₃ CF₃ H Br CH₃ O CH₂CH₃ F490 H H FCH₃ CF₃ H Cl CH₃ O CH₂CH₃ F491 H H F CH₃ CF₃ H CF₃ CH₃ O CH₂CH₃ F492 H HF CH₃ CF₃ H CH₃ CH₃ O CH₂CH₃ F493 H H F CH₃ CF₃ H Br CH₃ S CH₂CH₃ F494 HH F CH₃ CF₃ H Cl CH₃ S CH₂CH₃ F495 H H F CH₃ CF₃ H CF₃ CH₃ S CH₂CH₃ F496H H F CH₃ CF₃ H CH₃ CH₃ S CH₂CH₃ F497 H H F CH₃ CF₃ H Br H O CH₂CH₃ F498H H F CH₃ CF₃ H Cl H O CH₂CH₃ F499 H H F CH₃ CF₃ H CF₃ H O CH₂CH₃ F500 HH F CH₃ CF₃ H CH₃ H O CH₂CH₃ F501 H H F CH₃ CF₃ H Br H S CH₂CH₃ F502 H HF CH₃ CF₃ H Cl H S CH₂CH₃ F503 H H F CH₃ CF₃ H CF₃ H S CH₂CH₃ F504 H H FCH₃ CF₃ H CH₃ H S CH₂CH₃ F505 H H F CH₃ CF₃ CF₃ Br H O CH₂CF₃ F506 H H FCH₃ CF₃ CF₃ Cl H O CH₂CF₃ F507 H H F CH₃ CF₃ CF₃ CF₃ H O CH₂CF₃ F508 H HF CH₃ CF₃ CF₃ CH₃ H O CH₂CF₃ F509 H H F CH₃ CF₂CF₃ H Br H O CH₂CF₃ F510H H F CH₃ CF₂CF₃ H Cl H O CH₂CF₃ F511 H H F CH₃ CF₂CF₃ H CF₃ H O CH₂CF₃F512 H H F CH₃ CF₂CF₃ H CH₃ H O CH₂CF₃ F513 H H F CH₃ CF₃ H Br H OCH₂CF₃ F514 H H F CH₃ CF₃ H Cl H O CH₂CF₃ F515 H H F CH₃ CF₃ H CF₃ H OCH₂CF₃ F516 H H F CH₃ CF₃ H CH₃ H O CH₂CF₃ F517 H H F CH₃ CF₃ H Br H SCH₂CF₃ F518 H H F CH₃ CF₃ H Cl H S CH₂CF₃ F519 H H F CH₃ CF₃ H CF₃ H SCH₂CF₃ F520 H H F CH₃ CF₃ H CH₃ H S CH₂CF₃ F521 H H F Cl CF₃ H Br CH₃ OCH₂CH₃ F522 H H F Cl CF₃ H Cl CH₃ O CH₂CH₃ F523 H H F Cl CF₃ H CF₃ CH₃ OCH₂CH₃ F524 H H F Cl CF₃ H CH₃ CH₃ O CH₂CH₃ F525 H H F Cl CF₃ H Br CH₃ SCH₂CH₃ F526 H H F Cl CF₃ H Cl CH₃ S CH₂CH₃ F527 H H F Cl CF₃ H CF₃ CH₃ SCH₂CH₃ F528 H H F Cl CF₃ H CH₃ CH₃ S CH₂CH₃ F529 H H F Cl CF₃ H Br H OCH₂CH₃ F530 H H F Cl CF₃ H Cl H O CH₂CH₃ F531 H H F Cl CF₃ H CF₃ H OCH₂CH₃ F532 H H F Cl CF₃ H CH₃ H O CH₂CH₃ F533 H H F Cl CF₃ H Br H SCH₂CH₃ F534 H H F Cl CF₃ H Cl H S CH₂CH₃ F535 H H F Cl CF₃ H CF₃ H SCH₂CH₃ F536 H H F Cl CF₃ H CH₃ H S CH₂CH₃ F537 H H F Cl CF₃ CF₃ Br H OCH₂CF₃ F538 H H F Cl CF₃ CF₃ Cl H O CH₂CF₃ F539 H H F Cl CF₃ CF₃ CF₃ H OCH₂CF₃ F540 H H F Cl CF₃ CF₃ CH₃ H O CH₂CF₃ F541 H H F Cl CF₂CF₃ H Br HO CH₂CF₃ F542 H H F Cl CF₂CF₃ H Cl H O CH₂CF₃ F543 H H F Cl CF₂CF₃ H CF₃H O CH₂CF₃ F544 H H F Cl CF₂CF₃ H CH₃ H O CH₂CF₃ F545 H H F Cl CF₃ H BrH O CH₂CF₃ F546 H H F Cl CF₃ H Cl H O CH₂CF₃ F547 H H F Cl CF₃ H CF₃ H OCH₂CF₃ F548 H H F Cl CF₃ H CH₃ H O CH₂CF₃ F549 H H F Cl CF₃ H Br H SCH₂CF₃ F550 H H F Cl CF₃ H Cl H S CH₂CF₃ F551 H H F Cl CF₃ H CF₃ H SCH₂CF₃ F552 H H F Cl CF₃ H CH₃ H S CH₂CF₃ F553 H F F F CF₃ H Br CH₃ OCH₂CH₃ F554 H F F F CF₃ H Cl CH₃ O CH₂CH₃ F555 H F F F CF₃ H CF₃ CH₃ OCH₂CH₃ F556 H F F F CF₃ H CH₃ CH₃ O CH₂CH₃ F557 H F F F CF₃ H Br CH₃ SCH₂CH₃ F558 H F F F CF₃ H Cl CH₃ S CH₂CH₃ F559 H F F F CF₃ H CF₃ CH₃ SCH₂CH₃ F560 H F F F CF₃ H CH₃ CH₃ S CH₂CH₃ F561 H F F F CF₃ H Br H OCH₂CH₃ F562 H F F F CF₃ H Cl H O CH₂CH₃ F563 H F F F CF₃ H CF₃ H OCH₂CH₃ F564 H F F F CF₃ H CH₃ H O CH₂CH₃ F565 H F F F CF₃ H Br H SCH₂CH₃ F566 H F F F CF₃ H Cl H S CH₂CH₃ F567 H F F F CF₃ H CF₃ H SCH₂CH₃ F568 H F F F CF₃ H CH₃ H S CH₂CH₃ F569 H F F F CF₃ CF₃ Br H OCH₂CF₃ F570 H F F F CF₃ CF₃ Cl H O CH₂CF₃ F571 H F F F CF₃ CF₃ CF₃ H OCH₂CF₃ F572 H F F F CF₃ CF₃ CH₃ H O CH₂CF₃ F573 H F F F CF₂CF₃ H Br H OCH₂CF₃ F574 H F F F CF₂CF₃ H Cl H O CH₂CF₃ F575 H F F F CF₂CF₃ H CF₃ H OCH₂CF₃ F576 H F F F CF₂CF₃ H CH₃ H O CH₂CF₃ F577 H F F F CF₃ H Br H OCH₂CF₃ F578 H F F F CF₃ H Cl H O CH₂CF₃ F579 H F F F CF₃ H CF₃ H OCH₂CF₃ F580 H F F F CF₃ H CH₃ H O CH₂CF₃ F581 H F F F CF₃ H Br H SCH₂CF₃ F582 H F F F CF₃ H Cl H S CH₂CF₃ F583 H F F F CF₃ H CF₃ H SCH₂CF₃ F584 H F F F CF₃ H CH₃ H S CH₂CF₃ F585 H CF₃ H CF₃ CF₃ H Br CH₃ OCH₂CH₃ F586 H CF₃ H CF₃ CF₃ H Cl CH₃ O CH₂CH₃ F587 H CF₃ H CF₃ CF₃ H CF₃CH₃ O CH₂CH₃ F588 H CF₃ H CF₃ CF₃ H CH₃ CH₃ O CH₂CH₃ F589 H CF₃ H CF₃CF₃ H Br CH₃ S CH₂CH₃ F590 H CF₃ H CF₃ CF₃ H Cl CH₃ S CH₂CH₃ F591 H CF₃H CF₃ CF₃ H CF₃ CH₃ S CH₂CH₃ F592 H CF₃ H CF₃ CF₃ H CH₃ CH₃ S CH₂CH₃F593 H CF₃ H CF₃ CF₃ H Br H O CH₂CH₃ F594 H CF₃ H CF₃ CF₃ H Cl H OCH₂CH₃ F595 H CF₃ H CF₃ CF₃ H CF₃ H O CH₂CH₃ F596 H CF₃ H CF₃ CF₃ H CH₃H O CH₂CH₃ F597 H CF₃ H CF₃ CF₃ H Br H S CH₂CH₃ F598 H CF₃ H CF₃ CF₃ HCl H S CH₂CH₃ F599 H CF₃ H CF₃ CF₃ H CF₃ H S CH₂CH₃ F600 H CF₃ H CF₃ CF₃H CH₃ H S CH₂CH₃ F601 H CF₃ H CF₃ CF₃ CF₃ Br H O CH₂CF₃ F602 H CF₃ H CF₃CF₃ CF₃ Cl H O CH₂CF₃ F603 H CF₃ H CF₃ CF₃ CF₃ CF₃ H O CH₂CF₃ F604 H CF₃H CF₃ CF₃ CF₃ CH₃ H O CH₂CF₃ F605 H CF₃ H CF₃ CF₂CF₃ H Br H O CH₂CF₃F606 H CF₃ H CF₃ CF₂CF₃ H Cl H O CH₂CF₃ F607 H CF₃ H CF₃ CF₂CF₃ H CF₃ HO CH₂CF₃ F608 H CF₃ H CF₃ CF₂CF₃ H CH₃ H O CH₂CF₃ F609 H CF₃ H CF₃ CF₃ HBr H O CH₂CF₃ F610 H CF₃ H CF₃ CF₃ H Cl H O CH₂CF₃ F611 H CF₃ H CF₃ CF₃H CF₃ H O CH₂CF₃ F612 H CF₃ H CF₃ CF₃ H CH₃ H O CH₂CF₃ F613 H CF₃ H CF₃CF₃ H Br H S CH₂CF₃ F614 H CF₃ H CF₃ CF₃ H Cl H S CH₂CF₃ F615 H CF₃ HCF₃ CF₃ H CF₃ H S CH₂CF₃ F616 H CF₃ H CF₃ CF₃ H CH₃ H S CH₂CF₃ F617 H FH CF₃ CF₃ H Br CH₃ O CH₂CH₃ F618 H F H CF₃ CF₃ H Cl CH₃ O CH₂CH₃ F619 HF H CF₃ CF₃ H CF₃ CH₃ O CH₂CH₃ F620 H F H CF₃ CF₃ H CH₃ CH₃ O CH₂CH₃F621 H F H CF₃ CF₃ H Br CH₃ S CH₂CH₃ F622 H F H CF₃ CF₃ H Cl CH₃ SCH₂CH₃ F623 H F H CF₃ CF₃ H CF₃ CH₃ S CH₂CH₃ F624 H F H CF₃ CF₃ H CH₃CH₃ S CH₂CH₃ F625 H F H CF₃ CF₃ H Br H O CH₂CH₃ F626 H F H CF₃ CF₃ H ClH O CH₂CH₃ F627 H F H CF₃ CF₃ H CF₃ H O CH₂CH₃ F628 H F H CF₃ CF₃ H CH₃H O CH₂CH₃ F629 H F H CF₃ CF₃ H Br H S CH₂CH₃ F630 H F H CF₃ CF₃ H Cl HS CH₂CH₃ F631 H F H CF₃ CF₃ H CF₃ H S CH₂CH₃ F632 H F H CF₃ CF₃ H CH₃ HS CH₂CH₃ F633 H F H CF₃ CF₃ CF₃ Br H O CH₂CF₃ F634 H F H CF₃ CF₃ CF₃ ClH O CH₂CF₃ F635 H F H CF₃ CF₃ CF₃ CF₃ H O CH₂CF₃ F636 H F H CF₃ CF₃ CF₃CH₃ H O CH₂CF₃ F637 H F H CF₃ CF₂CF₃ H Br H O CH₂CF₃ F638 H F H CF₃CF₂CF₃ H Cl H O CH₂CF₃ F639 H F H CF₃ CF₂CF₃ H CF₃ H O CH₂CF₃ F640 H F HCF₃ CF₂CF₃ H CH₃ H O CH₂CF₃ F641 H F H CF₃ CF₃ H Br H O CH₂CF₃ F642 H FH CF₃ CF₃ H Cl H O CH₂CF₃ F643 H F H CF₃ CF₃ H CF₃ H O CH₂CF₃ F644 H F HCF₃ CF₃ H CH₃ H O CH₂CF₃ F645 H F H CF₃ CF₃ H Br H S CH₂CF₃ F646 H F HCF₃ CF₃ H Cl H S CH₂CF₃ F647 H F H CF₃ CF₃ H CF₃ H S CH₂CF₃ F648 H F HCF₃ CF₃ H CH₃ H S CH₂CF₃ F649 H Cl H CF₃ CF₃ H Br CH₃ O CH₂CH₃ F650 H ClH CF₃ CF₃ H Cl CH₃ O CH₂CH₃ F651 H Cl H CF₃ CF₃ H CF₃ CH₃ O CH₂CH₃ F652H Cl H CF₃ CF₃ H CH₃ CH₃ O CH₂CH₃ F653 H Cl H CF₃ CF₃ H Br CH₃ S CH₂CH₃F654 H Cl H CF₃ CF₃ H Cl CH₃ S CH₂CH₃ F655 H Cl H CF₃ CF₃ H CF₃ CH₃ SCH₂CH₃ F656 H Cl H CF₃ CF₃ H CH₃ CH₃ S CH₂CH₃ F657 H Cl H CF₃ CF₃ H Br HO CH₂CH₃ F658 H Cl H CF₃ CF₃ H Cl H O CH₂CH₃ F659 H Cl H CF₃ CF₃ H CF₃ HO CH₂CH₃ F660 H Cl H CF₃ CF₃ H CH₃ H O CH₂CH₃ F661 H Cl H CF₃ CF₃ H Br HS CH₂CH₃ F662 H Cl H CF₃ CF₃ H Cl H S CH₂CH₃ F663 H Cl H CF₃ CF₃ H CF₃ HS CH₂CH₃ F664 H Cl H CF₃ CF₃ H CH₃ H S CH₂CH₃ F665 H Cl H CF₃ CF₃ CF₃ BrH O CH₂CF₃ F666 H Cl H CF₃ CF₃ CF₃ Cl H O CH₂CF₃ F667 H Cl H CF₃ CF₃ CF₃CF₃ H O CH₂CF₃ F668 H Cl H CF₃ CF₃ CF₃ CH₃ H O CH₂CF₃ F669 H Cl H CF₃CF₂CF₃ H Br H O CH₂CF₃ F670 H Cl H CF₃ CF₂CF₃ H Cl H O CH₂CF₃ F671 H ClH CF₃ CF₂CF₃ H CF₃ H O CH₂CF₃ F672 H Cl H CF₃ CF₂CF₃ H CH₃ H O CH₂CF₃F673 H Cl H CF₃ CF₃ H Br H O CH₂CF₃ F674 H Cl H CF₃ CF₃ H Cl H O CH₂CF₃F675 H Cl H CF₃ CF₃ H CF₃ H O CH₂CF₃ F676 H Cl H CF₃ CF₃ H CH₃ H OCH₂CF₃ F677 H Cl H CF₃ CF₃ H Br H S CH₂CF₃ F678 H Cl H CF₃ CF₃ H Cl H SCH₂CF₃ F679 H Cl H CF₃ CF₃ H CF₃ H S CH₂CF₃ F680 H Cl H CF₃ CF₃ H CH₃ HS CH₂CF₃ F681 H H F CF₃ CF₃ H Br CH₃ O CH₂CH₃ F682 H H F CF₃ CF₃ H ClCH₃ O CH₂CH₃ F683 H H F CF₃ CF₃ H CF₃ CH₃ O CH₂CH₃ F684 H H F CF₃ CF₃ HCH₃ CH₃ O CH₂CH₃ F685 H H F CF₃ CF₃ H Br CH₃ S CH₂CH₃ F686 H H F CF₃ CF₃H Cl CH₃ S CH₂CH₃ F687 H H F CF₃ CF₃ H CF₃ CH₃ S CH₂CH₃ F688 H H F CF₃CF₃ H CH₃ CH₃ S CH₂CH₃ F689 H H F CF₃ CF₃ H Br H O CH₂CH₃ F690 H H F CF₃CF₃ H Cl H O CH₂CH₃ F691 H H F CF₃ CF₃ H CF₃ H O CH₂CH₃ F692 H H F CF₃CF₃ H CH₃ H O CH₂CH₃ F693 H H F CF₃ CF₃ H Br H S CH₂CH₃ F694 H H F CF₃CF₃ H Cl H S CH₂CH₃ F695 H H F CF₃ CF₃ H CF₃ H S CH₂CH₃ F696 H H F CF₃CF₃ H CH₃ H S CH₂CH₃ F697 H H F CF₃ CF₃ CF₃ Br H O CH₂CF₃ F698 H H F CF₃CF₃ CF₃ Cl H O CH₂CF₃ F699 H H F CF₃ CF₃ CF₃ CF₃ H O CH₂CF₃ F700 H H FCF₃ CF₃ CF₃ CH₃ H O CH₂CF₃ F701 H H F CF₃ CF₂CF₃ H Br H O CH₂CF₃ F702 HH F CF₃ CF₂CF₃ H Cl H O CH₂CF₃ F703 H H F CF₃ CF₂CF₃ H CF₃ H O CH₂CF₃F704 H H F CF₃ CF₂CF₃ H CH₃ H O CH₂CF₃ F705 H H F CF₃ CF₃ H Br H OCH₂CF₃ F706 H H F CF₃ CF₃ H Cl H O CH₂CF₃ F707 H H F CF₃ CF₃ H CF₃ H OCH₂CF₃ F708 H H F CF₃ CF₃ H CH₃ H O CH₂CF₃ F709 H H F CF₃ CF₃ H Br H SCH₂CF₃ F710 H H F CF₃ CF₃ H Cl H S CH₂CF₃ F711 H H F CF₃ CF₃ H CF₃ H SCH₂CF₃ F712 H H F CF₃ CF₃ H CH₃ H S CH₂CF₃ F713 H Cl Cl Cl CF₃ H Br CH₃S CH₂CH₃ F714 H Cl Cl Cl CF₃ H Cl CH₃ S CH₂CH₃ F715 H Cl Cl Cl CF₃ H CF₃CH₃ S CH₂CH₃ F716 H Cl Cl Cl CF₃ H CH₃ CH₃ S CH₂CH₃ F717 H Cl Cl Cl CF₃H Br H O CH₂CH₃ F718 H Cl Cl Cl CF₃ H Cl H O CH₂CH₃ F719 H Cl Cl Cl CF₃H CF₃ H O CH₂CH₃ F720 H Cl Cl Cl CF₃ H CH₃ H O CH₂CH₃ F721 H Cl Cl ClCF₃ H Br H S CH₂CH₃ F722 H Cl Cl Cl CF₃ H Cl H S CH₂CH₃ F723 H Cl Cl ClCF₃ H CF₃ H S CH₂CH₃ F724 H Cl Cl Cl CF₃ H CH₃ H S CH₂CH₃ F725 H Cl ClCl CF₃ CF₃ Br H O CH₂CF₃ F726 H Cl Cl Cl CF₃ CF₃ Cl H O CH₂CF₃ F727 H ClCl Cl CF₃ CF₃ CF₃ H O CH₂CF₃ F728 H Cl Cl Cl CF₃ CF₃ CH₃ H O CH₂CF₃ F729H Cl Cl Cl CF₂CF₃ H Br H O CH₂CF₃ F730 H Cl Cl Cl CF₂CF₃ H Cl H O CH₂CF₃F731 H Cl Cl Cl CF₂CF₃ H CF₃ H O CH₂CF₃ F732 H Cl Cl Cl CF₂CF₃ H CH₃ H OCH₂CF₃ F733 H Cl H Cl CF₃ H Br CH₃ O CH₂CH₃ F734 H Cl H Cl CF₃ H Cl CH₃O CH₂CH₃ F735 H Cl H Cl CF₃ H CF₃ CH₃ O CH₂CH₃ F736 H Cl H Cl CF₃ H CH₃CH₃ O CH₂CH₃ F737 H Cl H Cl CF₃ H Br CH₃ S CH₂CH₃ F738 H Cl H Cl CF₃ HCl CH₃ S CH₂CH₃ F739 H Cl H Cl CF₃ H CF₃ CH₃ S CH₂CH₃ F740 H Cl H Cl CF₃H CH₃ CH₃ S CH₂CH₃ F741 H Cl H Cl CF₃ H Br H O CH₂CH₃ F742 H Cl H Cl CF₃H Cl H O CH₂CH₃ F743 H Cl H Cl CF₃ H CF₃ H O CH₂CH₃ F744 H Cl H Cl CF₃ HCH₃ H O CH₂CH₃ F745 H Cl H Cl CF₃ H Br H S CH₂CH₃ F746 H Cl H Cl CF₃ HCl H S CH₂CH₃ F747 H Cl H Cl CF₃ H CF₃ H S CH₂CH₃ F748 H Cl H Cl CF₃ HCH₃ H S CH₂CH₃ F749 H Cl H Cl CF₃ CF₃ Br H O CH₂CF₃ F750 H Cl H Cl CF₃CF₃ Cl H O CH₂CF₃ F751 H Cl H Cl CF₃ CF₃ CF₃ H O CH₂CF₃ F752 H Cl H ClCF₃ CF₃ CH₃ H O CH₂CF₃ F753 H Cl H Cl CF₂CF₃ H Br H O CH₂CF₃ F754 H Cl HCl CF₂CF₃ H Cl H O CH₂CF₃ F755 H Cl H Cl CF₂CF₃ H CF₃ H O CH₂CF₃ F756 HCl H Cl CF₂CF₃ H CH₃ H O CH₂CF₃ F757 H Cl H Cl CF₃ H Br H O CH₂CF₃ F758H Cl H Cl CF₃ H Cl H O CH₂CF₃ F759 H Cl H Cl CF₃ H CF₃ H O CH₂CF₃ F760 HCl H Cl CF₃ H CH₃ H O CH₂CF₃ F761 H Cl H Cl CF₃ H Br H S CH₂CF₃ F762 HCl H Cl CF₃ H Cl H S CH₂CF₃ F763 H Cl H Cl CF₃ H CF₃ H S CH₂CF₃ F764 HCl H Cl CF₃ H CH₃ H S CH₂CF₃ F765 H H Cl Cl CF₃ H Br CH₃ O CH₂CH₃ F766 HH Cl Cl CF₃ H Cl CH₃ O CH₂CH₃ F767 H H Cl Cl CF₃ H CF₃ CH₃ O CH₂CH₃ F768H H Cl Cl CF₃ H CH₃ CH₃ O CH₂CH₃ F769 H H Cl Cl CF₃ H Br CH₃ S CH₂CH₃F770 H H Cl Cl CF₃ H Cl CH₃ S CH₂CH₃ F771 H H Cl Cl CF₃ H CF₃ CH₃ SCH₂CH₃ F772 H H Cl Cl CF₃ H CH₃ CH₃ S CH₂CH₃ F773 H H Cl Cl CF₃ H Br H OCH₂CH₃ F774 H H Cl Cl CF₃ H Cl H O CH₂CH₃ F775 H H Cl Cl CF₃ H CF₃ H OCH₂CH₃ F776 H H Cl Cl CF₃ H CH₃ H O CH₂CH₃ F777 H H Cl Cl CF₃ H Br H SCH₂CH₃ F778 H H Cl Cl CF₃ H Cl H S CH₂CH₃ F779 H H Cl Cl CF₃ H CF₃ H SCH₂CH₃ F780 H H Cl Cl CF₃ H CH₃ H S CH₂CH₃ F781 H H Cl Cl CF₃ CF₃ Br H OCH₂CF₃ F782 H H Cl Cl CF₃ CF₃ Cl H O CH₂CF₃ F783 H H Cl Cl CF₃ CF₃ CF₃ HO CH₂CF₃ F784 H H Cl Cl CF₃ CF₃ CH₃ H O CH₂CF₃ F785 H H Cl Cl CF₂CF₃ HBr H O CH₂CF₃ F786 H H Cl Cl CF₂CF₃ H Cl H O CH₂CF₃ F787 H H Cl ClCF₂CF₃ H CF₃ H O CH₂CF₃ F788 H H Cl Cl CF₂CF₃ H CH₃ H O CH₂CF₃ F789 H HCl Cl CF₃ H Br H O CH₂CF₃ F790 H H Cl Cl CF₃ H Cl H O CH₂CF₃ F791 H H ClCl CF₃ H CF₃ H O CH₂CF₃ F792 H H Cl Cl CF₃ H CH₃ H O CH₂CF₃ F793 H H ClCl CF₃ H Br H S CH₂CF₃ F794 H H Cl Cl CF₃ H Cl H S CH₂CF₃ F795 H H Cl ClCF₃ H CF₃ H S CH₂CF₃ F796 H H Cl Cl CF₃ H CH₃ H S CH₂CF₃ F797 H Cl F ClCF₃ H Br CH₃ O CH₂CH₃ F798 H Cl F Cl CF₃ H Cl CH₃ O CH₂CH₃ F799 H Cl FCl CF₃ H CF₃ CH₃ O CH₂CH₃ F800 H Cl F Cl CF₃ H CH₃ CH₃ O CH₂CH₃ F801 HCl F Cl CF₃ H Br CH₃ S CH₂CH₃ F802 H Cl F Cl CF₃ H Cl CH₃ S CH₂CH₃ F803H Cl F Cl CF₃ H CF₃ CH₃ S CH₂CH₃ F804 H Cl F Cl CF₃ H CH₃ CH₃ S CH₂CH₃F805 H Cl F Cl CF₃ H Br H O CH₂CH₃ F806 H Cl F Cl CF₃ H Cl H O CH₂CH₃F807 H Cl F Cl CF₃ H CF₃ H O CH₂CH₃ F808 H Cl F Cl CF₃ H CH₃ H O CH₂CH₃F809 H Cl F Cl CF₃ H Br H S CH₂CH₃ F810 H Cl F Cl CF₃ H Cl H S CH₂CH₃F811 H Cl F Cl CF₃ H CF₃ H S CH₂CH₃ F812 H Cl F Cl CF₃ H CH₃ H S CH₂CH₃F813 H Cl F Cl CF₃ CF₃ Cl H O CH₂CF₃ F814 H Cl F Cl CF₃ CF₃ CF₃ H OCH₂CF₃ F815 H Cl F Cl CF₃ CF₃ CH₃ H O CH₂CF₃ F816 H Cl F Cl CF₂CF₃ H BrH O CH₂CF₃ F817 H Cl F Cl CF₂CF₃ H Cl H O CH₂CF₃ F818 H Cl F Cl CF₂CF₃ HCF₃ H O CH₂CF₃ F819 H Cl F Cl CF₂CF₃ H CH₃ H O CH₂CF₃ F820 H Cl F Cl CF₃H Cl H O CH₂CF₃ F821 H Cl F Cl CF₃ H CF₃ H O CH₂CF₃ F822 H Cl F Cl CF₃ HCH₃ H O CH₂CF₃ F823 H Cl F Cl CF₃ H Cl H S CH₂CF₃ F824 H Cl F Cl CF₃ HCF₃ H S CH₂CF₃ F825 H Cl F Cl CF₃ H CH₃ H S CH₂CF₃ F826 H Br H Br CF₃ HCl CH₃ O CH₂CH₃ F827 H Br H Br CF₃ H CF₃ CH₃ O CH₂CH₃ F828 H Br H Br CF₃H CH₃ CH₃ O CH₂CH₃ F829 H Br H Br CF₃ H Br CH₃ S CH₂CH₃ F830 H Br H BrCF₃ H Cl CH₃ S CH₂CH₃ F831 H Br H Br CF₃ H CF₃ CH₃ S CH₂CH₃ F832 H Br HBr CF₃ H CH₃ CH₃ S CH₂CH₃ F833 H Br H Br CF₃ H Br H O CH₂CH₃ F834 H Br HBr CF₃ H Cl H O CH₂CH₃ F835 H Br H Br CF₃ H CF₃ H O CH₂CH₃ F836 H Br HBr CF₃ H CH₃ H O CH₂CH₃ F837 H Br H Br CF₃ H Br H S CH₂CH₃ F838 H Br HBr CF₃ H Cl H S CH₂CH₃ F839 H Br H Br CF₃ H CF₃ H S CH₂CH₃ F840 H Br HBr CF₃ H CH₃ H S CH₂CH₃ F841 H Br H Br CF₃ CF₃ Br H O CH₂CF₃ F842 H Br HBr CF₃ CF₃ Cl H O CH₂CF₃ F843 H Br H Br CF₃ CF₃ CF₃ H O CH₂CF₃ F844 H BrH Br CF₃ CF₃ CH₃ H O CH₂CF₃ F845 H Br H Br CF₂CF₃ H Br H O CH₂CF₃ F846 HBr H Br CF₂CF₃ H Cl H O CH₂CF₃ F847 H Br H Br CF₂CF₃ H CF₃ H O CH₂CF₃F848 H Br H Br CF₂CF₃ H CH₃ H O CH₂CF₃ F849 H Br H Br CF₃ H Cl H OCH₂CF₃ F850 H Br H Br CF₃ H CF₃ H O CH₂CF₃ F851 H Br H Br CF₃ H CH₃ H OCH₂CF₃ F852 H Br H Br CF₃ H Cl H S CH₂CF₃ F853 H Br H Br CF₃ H CF₃ H SCH₂CF₃ F854 H Br H Br CF₃ H CH₃ H S CH₂CF₃

Example A Bioassays on Beet Armyworm (“BAW”) and Corn Earworm (“CEW”)and Cabbage Looper (“CL”)

BAW has few effective parasites, diseases, or predators to lower itspopulation. BAW infests many weeds, trees, grasses, legumes, and fieldcrops. In various places, it is of economic concern upon asparagus,cotton, corn, soybeans, tobacco, alfalfa, sugar beets, peppers,tomatoes, potatoes, onions, peas, sunflowers, and citrus, among otherplants. CEW is known to attack corn and tomatoes, but it also attacksartichoke, asparagus, cabbage, cantaloupe, collards, cowpeas, cucumbers,eggplant, lettuce, lima beans, melon, okra, peas, peppers, potatoes,pumpkin, snap beans, spinach, squash, sweet potatoes, and watermelon,among other plants. CEW is also known to be resistant to certaininsecticides. CL feeds on a wide variety of cultivated plants and weeds.It feeds readily on crucifers, and has been reported damaging broccoli,cabbage, cauliflower, Chinese cabbage, collards, kale, mustard, radish,rutabaga, turnip, and watercress. Other vegetable crops injured includebeet, cantaloupe, celery, cucumber, lima bean, lettuce, parsnip, pea,pepper, potato, snap bean, spinach, squash, sweet potato, tomato, andwatermelon. CL is also known to be resistant to certain insecticides.Consequently, because of the above factors control of these pests isimportant. Furthermore, molecules that control these pests are useful incontrolling other pests.

Certain molecules disclosed in this document were tested against BAW andCEW and CL using procedures described in the following examples. In thereporting of the results, the “BAW & CEW & CL Rating Table” was used(See Table Section).

Bioassays on BAW (Spodoptera exigua)

Bioassays on BAW were conducted using a 128-well diet tray assay. one tofive second instar BAW larvae were placed in each well (3 mL) of thediet tray that had been previously filled with 1 mL of artificial dietto which 50 μg/cm² of the test compound (dissolved in 50 μL of 90:10acetone-water mixture) had been applied (to each of eight wells) andthen allowed to dry. Trays were covered with a clear self-adhesivecover, and held at 25° C., 14:10 light-dark for five to seven days.Percent mortality was recorded for the larvae in each well; activity inthe eight wells was then averaged. The results are indicated in thetable entitled “Table 3: Assay Results” (See Table Section).

Bioassays on CEW (Helicoverpa zea)

Bioassays on CEW were conducted using a 128-well diet tray assay. one tofive second instar CEW larvae were placed in each well (3 mL) of thediet tray that had been previously filled with 1 mL of artificial dietto which 50 μg/cm² of the test compound (dissolved in 50 μL of 90:10acetone-water mixture) had been applied (to each of eight wells) andthen allowed to dry. Trays were covered with a clear self-adhesivecover, and held at 25° C., 14:10 light-dark for five to seven days.Percent mortality was recorded for the larvae in each well; activity inthe eight wells was then averaged. The results are indicated in thetable entitled “Table 3: Assay Results” (See Table Section).

Bioassays on CL (Trichoplusia ni)

Bioassays on CL were conducted using a 128-well diet tray assay. One tofive second instar CL larvae were placed in each well (3 mL) of the diettray that had been previously filled with 1 mL of artificial diet towhich 50 μg/cm² of the test compound (dissolved in 50 μL of 90:10acetone-water mixture) had been applied (to each of eight wells) andthen allowed to dry. Trays were covered with a clear self-adhesivecover, and held at 25° C., 14:10 light-dark for five to seven days.Percent mortality was recorded for the larvae in each well; activity inthe eight wells was then averaged. The results are indicated in thetable entitled “Table 3A: Assay Results” (See Table Section).

Example B Bioassays on Green Peach Aphid (“GPA”) (Myzus persicae)

GPA is the most significant aphid pest of peach trees, causing decreasedgrowth, shriveling of the leaves, and the death of various tissues. Itis also hazardous because it acts as a vector for the transport of plantviruses, such as potato virus Y and potato leafroll virus to members ofthe nightshade/potato family Solanaceae, and various mosaic viruses tomany other food crops. GPA attacks such plants as broccoli, burdock,cabbage, carrot, cauliflower, daikon, eggplant, green beans, lettuce,macadamia, papaya, peppers, sweet potatoes, tomatoes, watercress, andzucchini, among other plants. GPA also attacks many ornamental cropssuch as carnation, chrysanthemum, flowering white cabbage, poinsettia,and roses. GPA has developed resistance to many pesticides.

Certain molecules disclosed in this document were tested against GPAusing procedures described in the following example. In the reporting ofthe results, the “GPA Rating Table” was used (See Table Section).

Cabbage seedlings grown in 3-inch pots, with 2-3 small (3-5 cm) trueleaves, were used as test substrate. The seedlings were infested with20-50 GPA (wingless adult and nymph stages) one day prior to chemicalapplication. Four pots with individual seedlings were used for eachtreatment. Test compounds (2 mg) were dissolved in 2 mL of acetone/MeOH(1:1) solvent, forming stock solutions of 1000 ppm test compound. Thestock solutions were diluted 5× with 0.025% Tween 20 in H₂O to obtainthe solution at 200 ppm test compound. A hand-held aspirator-typesprayer was used for spraying a solution to both sides of cabbage leavesuntil runoff. Reference plants (solvent check) were sprayed with thediluent only containing 20% by volume of acetone/MeOH (1:1) solvent.Treated plants were held in a holding room for three days atapproximately 25° C. and ambient relative humidity (RH) prior tograding. Evaluation was conducted by counting the number of live aphidsper plant under a microscope. Percent Control was measured by usingAbbott's correction formula (W. S. Abbott, “A Method of Computing theEffectiveness of an Insecticide” J. Econ. Entomol. 18 (1925), pp.265-267) as follows.

Corrected % Control=100*(X−Y)/X

-   -   where    -   X=No. of live aphids on solvent check plants and    -   Y=No. of live aphids on treated plants

The results are indicated in the table entitled “Table 3: Assay Results”(See Table Section).

Pesticidally Acceptable Acid Addition Salts, Salt Derivatives, Solvates,Ester Derivatives, Polymorphs, Isotopes and Radionuclides

Molecules of Formula One may be formulated into pesticidally acceptableacid addition salts. By way of a non-limiting example, an amine functioncan form salts with hydrochloric, hydrobromic, sulfuric, phosphoric,acetic, benzoic, citric, malonic, salicylic, malic, fumaric, oxalic,succinic, tartaric, lactic, gluconic, ascorbic, maleic, aspartic,benzenesulfonic, methanesulfonic, ethanesulfonic,hydroxymethanesulfonic, and hydroxyethanesulfonic acids. Additionally,by way of a non-limiting example, an acid function can form saltsincluding those derived from alkali or alkaline earth metals and thosederived from ammonia and amines. Examples of preferred cations includesodium, potassium, and magnesium.

Molecules of Formula One may be formulated into salt derivatives. By wayof a non-limiting example, a salt derivative can be prepared bycontacting a free base with a sufficient amount of the desired acid toproduce a salt. A free base may be regenerated by treating the salt witha suitable dilute aqueous base solution such as dilute aqueous sodiumhydroxide (NaOH), potassium carbonate, ammonia, and sodium bicarbonate.As an example, in many cases, a pesticide, such as 2,4-D, is made morewater-soluble by converting it to its dimethylamine salt.

Molecules of Formula One may be formulated into stable complexes with asolvent, such that the complex remains intact after the non-complexedsolvent is removed. These complexes are often referred to as “solvates.”However, it is particularly desirable to form stable hydrates with wateras the solvent.

Molecules of Formula One may be made into ester derivatives. These esterderivatives can then be applied in the same manner as the inventiondisclosed in this document is applied.

Molecules of Formula One may be made as various crystal polymorphs.Polymorphism is important in the development of agrochemicals sincedifferent crystal polymorphs or structures of the same molecule can havevastly different physical properties and biological performances.

Molecules of Formula One may be made with different isotopes. Ofparticular importance are molecules having ²H (also known as deuterium)in place of ¹H. Molecules of Formula One may be made with differentradionuclides. Of particular importance are molecules having ¹⁴C.

Stereoisomers

Molecules of Formula One may exist as one or more stereoisomers. Thus,certain molecules can be produced as racemic mixtures. It will beappreciated by those skilled in the art that one stereoisomer may bemore active than the other stereoisomers. Individual stereoisomers maybe obtained by known selective synthetic procedures, by conventionalsynthetic procedures using resolved starting materials, or byconventional resolution procedures. Certain molecules disclosed in thisdocument can exist as two or more isomers. The various isomers includegeometric isomers, diastereomers, and enantiomers. Thus, the moleculesdisclosed in this document include geometric isomers, racemic mixtures,individual stereoisomers, and optically active mixtures. It will beappreciated by those skilled in the art that one isomer may be moreactive than the others. The structures disclosed in the presentdisclosure are drawn in only one geometric form for clarity, but areintended to represent all geometric forms of the molecule.

Combinations

Molecules of Formula One may also be used in combination (such as, in acompositional mixture, or a simultaneous or sequential application) withone or more compounds having acaricidal, algicidal, avicidal,bactericidal, fungicidal, herbicidal, insecticidal, molluscicidal,nematicidal, rodenticidal, or virucidal properties. Additionally, themolecules of Formula One may also be used in combination (such as, in acompositional mixture, or a simultaneous or sequential application) withcompounds that are antifeedants, bird repellents, chemosterilants,herbicide safeners, insect attractants, insect repellents, mammalrepellents, mating disrupters, plant activators, plant growthregulators, or synergists. Examples of such compounds in the abovegroups that may be used with the Molecules of Formula Oneare—(3-ethoxypropyl)mercury bromide, 1,2-dichloropropane,1,3-dichloropropene, 1-methylcyclopropene, 1-naphthol,2-(octylthio)ethanol, 2,3,5-tri-iodobenzoic acid, 2,3,6-TBA,2,3,6-TBA-dimethylammonium, 2,3,6-TBA-lithium, 2,3,6-TBA-potassium,2,3,6-TBA-sodium, 2,4,5-T, 2,4,5-T-2-butoxypropyl, 2,4,5-T-2-ethylhexyl,2,4,5-T-3-butoxypropyl, 2,4,5-TB, 2,4,5-T-butomethyl, 2,4,5-T-butotyl,2,4,5-T-butyl, 2,4,5-T-isobutyl, 2,4,5-T-isoctyl, 2,4,5-T-isopropyl,2,4,5-T-methyl, 2,4,5-T-pentyl, 2,4,5-T-sodium,2,4,5-T-triethylammonium, 2,4,5-T-trolamine, 2,4-D,2,4-D-2-butoxypropyl, 2,4-D-2-ethylhexyl, 2,4-D-3-butoxypropyl,2,4-D-ammonium, 2,4-DB, 2,4-DB-butyl, 2,4-DB-dimethylammonium,2,4-DB-isoctyl, 2,4-DB-potassium, 2,4-DB-sodium, 2,4-D-butotyl,2,4-D-butyl, 2,4-D-diethylammonium, 2,4-D-dimethylammonium,2,4-D-diolamine, 2,4-D-dodecylammonium, 2,4-DEB, 2,4-DEP, 2,4-D-ethyl,2,4-D-heptylammonium, 2,4-D-isobutyl, 2,4-D-isoctyl, 2,4-D-isopropyl,2,4-D-isopropylammonium, 2,4-D-lithium, 2,4-D-meptyl, 2,4-D-methyl,2,4-D-octyl, 2,4-D-pentyl, 2,4-D-potassium, 2,4-D-propyl, 2,4-D-sodium,2,4-D-tefuryl, 2,4-D-tetradecylammonium, 2,4-D-triethylammonium,2,4-D-tris(2-hydroxypropyl)ammonium, 2,4-D-trolamine, 2iP,2-methoxyethylmercury chloride, 2-phenylphenol, 3,4-DA, 3,4-DB, 3,4-DP,4-aminopyridine, 4-CPA, 4-CPA-potassium, 4-CPA-sodium, 4-CPB, 4-CPP,4-hydroxyphenethyl alcohol, 8-hydroxyquinoline sulfate,8-phenylmercurioxyquinoline, abamectin, abscisic acid, ACC, acephate,acequinocyl, acetamiprid, acethion, acetochlor, acetophos, acetoprole,acibenzolar, acibenzolar-5-methyl, acifluorfen, acifluorfen-methyl,acifluorfen-sodium, aclonifen, acrep, acrinathrin, acrolein,acrylonitrile, acypetacs, acypetacs-copper, acypetacs-zinc, alachlor,alanycarb, albendazole, aldicarb, aldimorph, aldoxycarb, aldrin,allethrin, allicin, allidochlor, allosamidin, alloxydim,alloxydim-sodium, allyl alcohol, allyxycarb, alorac, alpha-cypermethrin,alpha-endosulfan, ametoctradin, ametridione, ametryn, amibuzin,amicarbazone, amicarthiazol, amidithion, amidoflumet, amidosulfuron,aminocarb, aminocyclopyrachlor, aminocyclopyrachlor-methyl,aminocyclopyrachlor-potassium, aminopyralid, aminopyralid-potassium,aminopyralid-tris(2-hydroxypropyl)ammonium, amiprofos-methyl,amiprophos, amisulbrom, amiton, amiton oxalate, amitraz, amitrole,ammonium sulfamate, ammonium α-naphthaleneacetate, amobam, ampropylfos,anabasine, ancymidol, anilazine, anilofos, anisuron, anthraquinone,antu, apholate, aramite, arsenous oxide, asomate, aspirin, asulam,asulam-potassium, asulam-sodium, athidathion, atraton, atrazine,aureofungin, aviglycine, aviglycine hydrochloride, azaconazole,azadirachtin, azafenidin, azamethiphos, azimsulfuron, azinphos-ethyl,azinphos-methyl, aziprotryne, azithiram, azobenzene, azocyclotin,azothoate, azoxystrobin, bachmedesh, barban, barium hexafluorosilicate,barium polysulfide, barthrin, BCPC, beflubutamid, benalaxyl,benalaxyl-M, benazolin, benazolin-dimethylammonium, benazolin-ethyl,benazolin-potassium, bencarbazone, benclothiaz, bendiocarb, benfluralin,benfuracarb, benfuresate, benodanil, benomyl, benoxacor, benoxafos,benquinox, bensulfuron, bensulfuron-methyl, bensulide, bensultap,bentaluron, bentazone, bentazone-sodium, benthiavalicarb,benthiavalicarb-isopropyl, benthiazole, bentranil, benzadox,benzadox-ammonium, benzalkonium chloride, benzamacril,benzamacril-isobutyl, benzamorf, benzfendizone, benzipram,benzobicyclon, benzofenap, benzofluor, benzohydroxamic acid,benzoximate, benzoylprop, benzoylprop-ethyl, benzthiazuron, benzylbenzoate, benzyladenine, berberine, berberine chloride, beta-cyfluthrin,beta-cypermethrin, bethoxazin, bicyclopyrone, bifenazate, bifenox,bifenthrin, bifujunzhi, bilanafos, bilanafos-sodium, binapacryl,bingqingxiao, bioallethrin, bioethanomethrin, biopermethrin,bioresmethrin, biphenyl, bisazir, bismerthiazol, bispyribac,bispyribac-sodium, bistrifluoron, bitertanol, bithionol, bixafen,blasticidin-S, borax, Bordeaux mixture, boric acid, boscalid,brassinolide, brassinolide-ethyl, brevicomin, brodifacoum,brofenvalerate, brofluthrinate, bromacil, bromacil-lithium,bromacil-sodium, bromadiolone, bromethalin, bromethrin, bromfenvinfos,bromoacetamide, bromobonil, bromobutide, bromocyclen, bromo-DDT,bromofenoxim, bromophos, bromophos-ethyl, bromopropylate, bromothalonil,bromoxynil, bromoxynil butyrate, bromoxynil heptanoate, bromoxyniloctanoate, bromoxynil-potassium, brompyrazon, bromuconazole, bronopol,bucarpolate, bufencarb, buminafos, bupirimate, buprofezin, Burgundymixture, busulfan, butacarb, butachlor, butafenacil, butamifos,butathiofos, butenachlor, butethrin, buthidazole, buthiobate, buthiuron,butocarboxim, butonate, butopyronoxyl, butoxycarboxim, butralin,butroxydim, buturon, butylamine, butylate, cacodylic acid, cadusafos,cafenstrole, calcium arsenate, calcium chlorate, calcium cyanamide,calcium polysulfide, calvinphos, cambendichlor, camphechlor, camphor,captafol, captan, carbamorph, carbanolate, carbaryl, carbasulam,carbendazim, carbendazim benzenesulfonate, carbendazim sulfite,carbetamide, carbofuran, carbon disulfide, carbon tetrachloride,carbophenothion, carbosulfan, carboxazole, carboxide, carboxin,carfentrazone, carfentrazone-ethyl, carpropamid, cartap, cartaphydrochloride, carvacrol, carvone, CDEA, cellocidin, CEPC, ceralure,Cheshunt mixture, chinomethionat, chitosan, chlobenthiazone,chlomethoxyfen, chloralose, chloramben, chloramben-ammonium,chloramben-diolamine, chloramben-methyl, chloramben-methylammonium,chloramben-sodium, chloramine phosphorus, chloramphenicol,chloraniformethan, chloranil, chloranocryl, chlorantraniliprole,chlorazifop, chlorazifop-propargyl, chlorazine, chlorbenside,chlorbenzuron, chlorbicyclen, chlorbromuron, chlorbufam, chlordane,chlordecone, chlordimeform, chlordimeform hydrochloride,chlorempenthrin, chlorethoxyfos, chloreturon, chlorfenac,chlorfenac-ammonium, chlorfenac-sodium, chlorfenapyr, chlorfenazole,chlorfenethol, chlorfenprop, chlorfenson, chlorfensulphide,chlorfenvinphos, chlorfluazuron, chlorflurazole, chlorfluren,chlorfluren-methyl, chlorflurenol, chlorflurenol-methyl, chloridazon,chlorimuron, chlorimuron-ethyl, chlormephos, chlormequat, chlormequatchloride, chlomidine, chlornitrofen, chlorobenzilate,chlorodinitronaphthalenes, chloroform, chloromebuform, chloromethiuron,chloroneb, chlorophacinone, chlorophacinone-sodium, chloropicrin,chloropon, chloropropylate, chlorothalonil, chlorotoluron, chloroxuron,chloroxynil, chlorphonium, chlorphonium chloride, chlorphoxim,chlorprazophos, chlorprocarb, chlorpropham, chlorpyrifos,chlorpyrifos-methyl, chlorquinox, chlorsulfuron, chlorthal,chlorthal-dimethyl, chlorthal-monomethyl, chlorthiamid, chlorthiophos,chlozolinate, choline chloride, chromafenozide, cinerin I, cinerin II,cinerins, cinidon-ethyl, cinmethylin, cinosulfuron, ciobutide,cisanilide, cismethrin, clethodim, climbazole, cliodinate, clodinafop,clodinafop-propargyl, cloethocarb, clofencet, clofencet-potassium,clofentezine, clofibric acid, clofop, clofop-isobutyl, clomazone,clomeprop, cloprop, cloproxydim, clopyralid, clopyralid-methyl,clopyralid-olamine, clopyralid-potassium,clopyralid-tris(2-hydroxypropyl)ammonium, cloquintocet,cloquintocet-mexyl, cloransulam, cloransulam-methyl, closantel,clothianidin, clotrimazole, cloxyfonac, cloxyfonac-sodium, CMA,codlelure, colophonate, copper acetate, copper acetoarsenite, copperarsenate, copper carbonate, basic, copper hydroxide, copper naphthenate,copper oleate, copper oxychloride, copper silicate, copper sulfate,copper zinc chromate, coumachlor, coumafuryl, coumaphos, coumatetralyl,coumithoate, coumoxystrobin, CPMC, CPMF, CPPC, credazine, cresol,crimidine, crotamiton, crotoxyphos, crufomate, cryolite, cue-lure,cufraneb, cumyluron, cuprobam, cuprous oxide, curcumenol, cyanamide,cyanatryn, cyanazine, cyanofenphos, cyanophos, cyanthoate,cyantraniliprole, cyazofamid, cybutryne, cyclafuramid, cyclanilide,cyclethrin, cycloate, cycloheximide, cycloprate, cycloprothrin,cyclosulfamuron, cycloxaprid, cycloxydim, cycluron, cyenopyrafen,cyflufenamid, cyflumetofen, cyfluthrin, cyhalofop, cyhalofop-butyl,cyhalothrin, cyhexatin, cymiazole, cymiazole hydrochloride, cymoxanil,cyometrinil, cypendazole, cypermethrin, cyperquat, cyperquat chloride,cyphenothrin, cyprazine, cyprazole, cyproconazole, cyprodinil,cyprofuram, cypromid, cyprosulfamide, cyromazine, cythioate, daimuron,dalapon, dalapon-calcium, dalapon-magnesium, dalapon-sodium, daminozide,dayoutong, dazomet, dazomet-sodium, DB CP, d-camphor, DCIP, DCPTA, DDT,debacarb, decafentin, decarbofuran, dehydroacetic acid, delachlor,deltamethrin, demephion, demephion-O, demephion-S, demeton,demeton-methyl, demeton-O, demeton-O-methyl, demeton-S,demeton-S-methyl, demeton-S-methylsulphon, desmedipham, desmetryn,d-fanshiluquebingjuzhi, diafenthiuron, dialifos, di-allate, diamidafos,diatomaceous earth, diazinon, dibutyl phthalate, dibutyl succinate,dicamba, dicamba-diglycolamine, dicamba-dimethylammonium,dicamba-diolamine, dicamba-isopropylammonium, dicamba-methyl,dicamba-olamine, dicamba-potassium, dicamba-sodium, dicamba-trolamine,dicapthon, dichlobenil, dichlofenthion, dichlofluanid, dichlone,dichloralurea, dichlorbenzuron, dichlorflurenol, dichlorflurenol-methyl,dichlormate, dichlormid, dichlorophen, dichlorprop,dichlorprop-2-ethylhexyl, dichlorprop-butotyl,dichlorprop-dimethylammonium, dichlorprop-ethylammonium,dichlorprop-isoctyl, dichlorprop-methyl, dichlorprop-P,dichlorprop-P-2-ethylhexyl, dichlorprop-P-dimethylammonium,dichlorprop-potassium, dichlorprop-sodium, dichlorvos, dichlozoline,diclobutrazol, diclocymet, diclofop, diclofop-methyl, diclomezine,diclomezine-sodium, dicloran, diclosulam, dicofol, dicoumarol, dicresyl,dicrotophos, dicyclanil, dicyclonon, dieldrin, dienochlor, diethamquat,diethamquat dichloride, diethatyl, diethatyl-ethyl, diethofencarb,dietholate, diethyl pyrocarbonate, diethyltoluamide, difenacoum,difenoconazole, difenopenten, difenopenten-ethyl, difenoxuron,difenzoquat, difenzoquat metilsulfate, difethialone, diflovidazin,diflubenzuron, diflufenican, diflufenzopyr, diflufenzopyr-sodium,diflumetorim, dikegulac, dikegulac-sodium, dilor, dimatif, dimefluthrin,dimefox, dimefuron, dimepiperate, dimetachlone, dimetan, dimethacarb,dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimethipin,dimethirimol, dimethoate, dimethomorph, dimethrin, dimethyl carbate,dimethyl phthalate, dimethylvinphos, dimetilan, dimexano, dimidazon,dimoxystrobin, dinex, dinex-diclexine, dingjunezuo, diniconazole,diniconazole-M, dinitramine, dinobuton, dinocap, dinocap-4, dinocap-6,dinocton, dinofenate, dinopenton, dinoprop, dinosam, dinoseb, dinosebacetate, dinoseb-ammonium, dinoseb-diolamine, dinoseb-sodium,dinoseb-trolamine, dinosulfon, dinotefuran, dinoterb, dinoterb acetate,dinoterbon, diofenolan, dioxabenzofos, dioxacarb, dioxathion,diphacinone, diphacinone-sodium, diphenamid, diphenyl sulfone,diphenylamine, dipropalin, dipropetryn, dipyrithione, diquat, diquatdibromide, disparlure, disul, disulfuram, disulfoton, disul-sodium,ditalimfos, dithianon, dithicrofos, dithioether, dithiopyr, diuron,d-limonene, DMPA, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium,dodemorph, dodemorph acetate, dodemorph benzoate, dodicin, dodicinhydrochloride, dodicin-sodium, dodine, dofenapyn, dominicalure,doramectin, drazoxolon, DSMA, dufulin, EBEP, EBP, ecdysterone,edifenphos, eglinazine, eglinazine-ethyl, emamectin, emamectin benzoate,EMPC, empenthrin, endosulfan, endothal, endothal-diammonium,endothal-dipotassium, endothal-disodium, endothion, endrin,enestroburin, EPN, epocholeone, epofenonane, epoxiconazole,eprinomectin, epronaz, EPTC, erbon, ergocalciferol, erlujixiancaoan,esdépalléthrine, esfenvalerate, esprocarb, etacelasil, etaconazole,etaphos, etem, ethaboxam, ethachlor, ethalfluralin, ethametsulfuron,ethametsulfuron-methyl, ethaprochlor, ethephon, ethidimuron,ethiofencarb, ethiolate, ethion, ethiozin, ethiprole, ethirimol,ethoate-methyl, ethofumesate, ethohexadiol, ethoprophos, ethoxyfen,ethoxyfen-ethyl, ethoxyquin, ethoxysulfuron, ethychlozate, ethylformate, ethyl α-naphthaleneacetate, ethyl-DDD, ethylene, ethylenedibromide, ethylene dichloride, ethylene oxide, ethylicin, ethylmercury2,3-dihydroxypropyl mercaptide, ethylmercury acetate, ethylmercurybromide, ethylmercury chloride, ethylmercury phosphate, etinofen,etnipromid, etobenzanid, etofenprox, etoxazole, etridiazole, etrimfos,eugenol, EXD, famoxadone, famphur, fenamidone, fenaminosulf, fenamiphos,fenapanil, fenarimol, fenasulam, fenazaflor, fenazaquin, fenbuconazole,fenbutatin oxide, fenchlorazole, fenchlorazole-ethyl, fenchlorphos,fenclorim, fenethacarb, fenfluthrin, fenfuram, fenhexamid, fenitropan,fenitrothion, fenjuntong, fenobucarb, fenoprop, fenoprop-3-butoxypropyl,fenoprop-butomethyl, fenoprop-butotyl, fenoprop-butyl, fenoprop-isoctyl,fenoprop-methyl, fenoprop-potassium, fenothiocarb, fenoxacrim,fenoxanil, fenoxaprop, fenoxaprop-ethyl, fenoxaprop-P,fenoxaprop-P-ethyl, fenoxasulfone, fenoxycarb, fenpiclonil,fenpirithrin, fenpropathrin, fenpropidin, fenpropimorph, fenpyrazamine,fenpyroximate, fenridazon, fenridazon-potassium, fenridazon-propyl,fenson, fensulfothion, fenteracol, fenthiaprop, fenthiaprop-ethyl,fenthion, fenthion-ethyl, fentin, fentin acetate, fentin chloride,fentin hydroxide, fentrazamide, fentrifanil, fenuron, fenuron TCA,fenvalerate, ferbam, ferimzone, ferrous sulfate, fipronil, flamprop,flamprop-isopropyl, flamprop-M, flamprop-methyl, flamprop-M-isopropyl,flamprop-M-methyl, flazasulfuron, flocoumafen, flometoquin, flonicamid,florasulam, fluacrypyrim, fluazifop, fluazifop-butyl, fluazifop-methyl,fluazifop-P, fluazifop-P-butyl, fluazinam, fluazolate, fluazuron,flubendiamide, flubenzimine, flucarbazone, flucarbazone-sodium,flucetosulfuron, fluchloralin, flucofuron, flucycloxuron, flucythrinate,fludioxonil, fluenetil, fluensulfone, flufenacet, flufenerim,flufenican, flufenoxuron, flufenprox, flufenpyr, flufenpyr-ethyl,flufiprole, flumethrin, flumetover, flumetralin, flumetsulam, flumezin,flumiclorac, flumiclorac-pentyl, flumioxazin, flumipropyn, flumorph,fluometuron, fluopicolide, fluopyram, fluorbenside, fluoridamid,fluoroacetamide, fluorodifen, fluoroglycofen, fluoroglycofen-ethyl,fluoroimide, fluoromidine, fluoronitrofen, fluothiuron, fluotrimazole,fluoxastrobin, flupoxam, flupropacil, flupropadine, flupropanate,flupropanate-sodium, flupyradifurone, flupyrsulfuron,flupyrsulfuron-methyl, flupyrsulfuron-methyl-sodium, fluquinconazole,flurazole, flurenol, flurenol-butyl, flurenol-methyl, fluridone,fluorochloridone, fluoroxypyr, fluoroxypyr-butomethyl,fluoroxypyr-meptyl, flurprimidol, flursulamid, flurtamone, flusilazole,flusulfamide, fluthiacet, fluthiacet-methyl, flutianil, flutolanil,flutriafol, fluvalinate, fluxapyroxad, fluxofenim, folpet, fomesafen,fomesafen-sodium, fonofos, foramsulfuron, forchlorfenuron, formaldehyde,formetanate, formetanate hydrochloride, formothion, formparanate,formparanate hydrochloride, fosamine, fosamine-ammonium, fosetyl,fosetyl-aluminium, fosmethilan, fospirate, fosthiazate, fosthietan,frontalin, fuberidazole, fucaojing, fucaomi, funaihecaoling,fuphenthiourea, furalane, furalaxyl, furamethrin, furametpyr,furathiocarb, furcarbanil, furconazole, furconazole-cis, furethrin,furfural, furilazole, furmecyclox, furophanate, furyloxyfen,gamma-cyhalothrin, gamma-HCH, genit, gibberellic acid, gibberellins,gliftor, glufosinate, glufosinate-ammonium, glufosinate-P,glufosinate-P-ammonium, glufosinate-P-sodium, glyodin, glyoxime,glyphosate, glyphosate-diammonium, glyphosate-dimethylammonium,glyphosate-isopropylammonium, glyphosate-monoammonium,glyphosate-potassium, glyphosate-sesquisodium, glyphosate-trimesium,glyphosine, gossyplure, grandlure, griseofulvin, guazatine, guazatineacetates, halacrinate, halfenprox, halofenozide, halosafen,halosulfuron, halosulfuron-methyl, haloxydine, haloxyfop,haloxyfop-etotyl, haloxyfop-methyl, haloxyfop-P, haloxyfop-P-etotyl,haloxyfop-P-methyl, haloxyfop-sodium, HCH, hemel, hempa, HEOD,heptachlor, heptenophos, heptopargil, heterophos, hexachloroacetone,hexachlorobenzene, hexachlorobutadiene, hexachlorophene, hexaconazole,hexaflumuron, hexaflurate, hexylure, hexamide, hexazinone, hexylthiofos,hexythiazox, HHDN, holosulf, huancaiwo, huangcaoling, huanjunzuo,hydramethylnon, hydrargaphen, hydrated lime, hydrogen cyanide,hydroprene, hymexazol, hyquincarb, IAA, IBA, icaridin, imazalil,imazalil nitrate, imazalil sulfate, imazamethabenz,imazamethabenz-methyl, imazamox, imazamox-ammonium, imazapic,imazapic-ammonium, imazapyr, imazapyr-isopropylammonium, imazaquin,imazaquin-ammonium, imazaquin-methyl, imazaquin-sodium, imazethapyr,imazethapyr-ammonium, imazosulfuron, imibenconazole, imicyafos,imidacloprid, imidaclothiz, iminoctadine, iminoctadine triacetate,iminoctadine trialbesilate, imiprothrin, inabenfide, indanofan,indaziflam, indoxacarb, inezin, iodobonil, iodocarb, iodomethane,iodosulfuron, iodosulfuron-methyl, iodosulfuron-methyl-sodium,iofensulfuron, iofensulfuron-sodium, ioxynil, ioxynil octanoate,ioxynil-lithium, ioxynil-sodium, ipazine, ipconazole, ipfencarbazone,iprobenfos, iprodione, iprovalicarb, iprymidam, ipsdienol, ipsenol,IPSP, isamidofos, isazofos, isobenzan, isocarbamid, isocarbophos,isocil, isodrin, isofenphos, isofenphos-methyl, isolan, isomethiozin,isonoruron, isopolinate, isoprocarb, isopropalin, isoprothiolane,isoproturon, isopyrazam, isopyrimol, isothioate, isotianil, isouron,isovaledione, isoxaben, isoxachlortole, isoxadifen, isoxadifen-ethyl,isoxaflutole, isoxapyrifop, isoxathion, ivermectin, izopamfos,japonilure, japothrins, jasmolin I, jasmolin II, jasmonic acid,jiahuangchongzong, jiajizengxiaolin, jiaxiangjunzhi, jiecaowan,jiecaoxi, jodfenphos, juvenile hormone I, juvenile hormone II, juvenilehormone III, kadethrin, karbutilate, karetazan, karetazan-potassium,kasugamycin, kasugamycin hydrochloride, kejunlin, kelevan, ketospiradox,ketospiradox-potassium, kinetin, kinoprene, kresoxim-methyl, kuicaoxi,lactofen, lambda-cyhalothrin, latilure, lead arsenate, lenacil,lepimectin, leptophos, lindane, lineatin, linuron, lirimfos, litlure,looplure, lufenuron, lvdingjunzhi, lvxiancaolin, lythidathion, MAA,malathion, maleic hydrazide, malonoben, maltodextrin, MAMA, mancopper,mancozeb, mandipropamid, maneb, matrine, mazidox, MCPA,MCPA-2-ethylhexyl, MCPA-butotyl, MCPA-butyl, MCPA-dimethylammonium,MCPA-diolamine, MCPA-ethyl, MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl,MCPA-methyl, MCPA-olamine, MCPA-potassium, MCPA-sodium, MCPA-thioethyl,MCPA-trolamine, MCPB, MCPB-ethyl, MCPB-methyl, MCPB-sodium, mebenil,mecarbam, mecarbinzid, mecarphon, mecoprop, mecoprop-2-ethylhexyl,mecoprop-dimethylammonium, mecoprop-diolamine, mecoprop-ethadyl,mecoprop-isoctyl, mecoprop-methyl, mecoprop-P, mecoprop-P-2-ethylhexyl,mecoprop-P-dimethylammonium, mecoprop-P-isobutyl, mecoprop-potassium,mecoprop-P-potassium, mecoprop-sodium, mecoprop-trolamine, medimeform,medinoterb, medinoterb acetate, medlure, mefenacet, mefenpyr,mefenpyr-diethyl, mefluidide, mefluidide-diolamine,mefluidide-potassium, megatomoic acid, menazon, mepanipyrim,meperfluthrin, mephenate, mephosfolan, mepiquat, mepiquat chloride,mepiquat pentaborate, mepronil, meptyldinocap, mercuric chloride,mercuric oxide, mercurous chloride, merphos, mesoprazine, mesosulfuron,mesosulfuron-methyl, mesotrione, mesulfen, mesulfenfos, metaflumizone,metalaxyl, metalaxyl-M, metaldehyde, metam, metam-ammonium, metamifop,metamitron, metam-potassium, metam-sodium, metazachlor, metazosulfuron,metazoxolon, metconazole, metepa, metflurazon, methabenzthiazuron,methacrifos, methalpropalin, methamidophos, methasulfocarb, methazole,methfuroxam, methidathion, methiobencarb, methiocarb,methiopyrisulfuron, methiotepa, methiozolin, methiuron, methocrotophos,methometon, methomyl, methoprene, methoprotryne, methoquin-butyl,methothrin, methoxychlor, methoxyfenozide, methoxyphenone, methylapholate, methyl bromide, methyl eugenol, methyl iodide, methylisothiocyanate, methylacetophos, methylchloroform, methyldymron,methylene chloride, methylmercury benzoate, methylmercury dicyandiamide,methylmercury pentachlorophenoxide, methylneodecanamide, metiram,metobenzuron, metobromuron, metofluthrin, metolachlor, metolcarb,metominostrobin, metosulam, metoxadiazone, metoxuron, metrafenone,metribuzin, metsulfovax, metsulfuron, metsulfuron-methyl, mevinphos,mexacarbate, mieshuan, milbemectin, milbemycin oxime, milneb, mipafox,mirex, MNAF, moguchun, molinate, molosultap, monalide, monisouron,monochloroacetic acid, monocrotophos, monolinuron, monosulfuron,monosulfuron-ester, monuron, monuron TCA, morfamquat, morfamquatdichloride, moroxydine, moroxydine hydrochloride, morphothion, morzid,moxidectin, MSMA, muscalure, myclobutanil, myclozolin,N-(ethylmercury)-p-toluenesulphonanilide, nabam, naftalofos, naled,naphthalene, naphthaleneacetamide, naphthalic anhydride, naphthoxyaceticacids, naproanilide, napropamide, naptalam, naptalam-sodium, natamycin,neburon, niclosamide, niclosamide-olamine, nicosulfuron, nicotine,nifluridide, nipyraclofen, nitenpyram, nithiazine, nitralin, nitrapyrin,nitrilacarb, nitrofen, nitrofluorfen, nitrostyrene, nitrothal-isopropyl,norbormide, norflurazon, nomicotine, noruron, novaluron, noviflumuron,nuarimol, OCH, octachlorodipropyl ether, octhilinone, ofurace,omethoate, orbencarb, orfralure, ortho-dichlorobenzene, orthosulfamuron,oryctalure, orysastrobin, oryzalin, osthol, ostramone, oxabetrinil,oxadiargyl, oxadiazon, oxadixyl, oxamate, oxamyl, oxapyrazon,oxapyrazon-dimolamine, oxapyrazon-sodium, oxasulfuron, oxaziclomefone,oxine-copper, oxolinic acid, oxpoconazole, oxpoconazole fumarate,oxycarboxin, oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxyfluorfen,oxymatrine, oxytetracycline, oxytetracycline hydrochloride,paclobutrazol, paichongding, para-dichlorobenzene, parafluoron,paraquat, paraquat dichloride, paraquat dimetilsulfate, parathion,parathion-methyl, parinol, pebulate, pefurazoate, pelargonic acid,penconazole, pencycuron, pendimethalin, penflufen, penfluoron,penoxsulam, pentachlorophenol, pentanochlor, penthiopyrad, pentmethrin,pentoxazone, perfluidone, permethrin, pethoxamid, phenamacril, phenazineoxide, phenisopham, phenkapton, phenmedipham, phenmedipham-ethyl,phenobenzuron, phenothrin, phenproxide, phenthoate, phenylmercuriurea,phenylmercury acetate, phenylmercury chloride, phenylmercury derivativeof pyrocatechol, phenylmercury nitrate, phenylmercury salicylate,phorate, phosacetim, phosalone, phosdiphen, phosfolan, phosfolan-methyl,phosglycin, phosmet, phosnichlor, phosphamidon, phosphine, phosphocarb,phosphorus, phostin, phoxim, phoxim-methyl, phthalide, picloram,picloram-2-ethylhexyl, picloram-isoctyl, picloram-methyl,picloram-olamine, picloram-potassium, picloram-triethylammonium,picloram-tris(2-hydroxypropyl)ammonium, picolinafen, picoxystrobin,pindone, pindone-sodium, pinoxaden, piperalin, piperonyl butoxide,piperonyl cyclonene, piperophos, piproctanyl, piproctanyl bromide,piprotal, pirimetaphos, pirimicarb, pirimioxyphos, pirimiphos-ethyl,pirimiphos-methyl, plifenate, polycarbamate, polyoxins, polyoxorim,polyoxorim-zinc, polythialan, potassium arsenite, potassium azide,potassium cyanate, potassium gibberellate, potassium naphthenate,potassium polysulfide, potassium thiocyanate, potassiumα-naphthaleneacetate, pp′-DDT, prallethrin, precocene I, precocene II,precocene III, pretilachlor, primidophos, primisulfuron,primisulfuron-methyl, probenazole, prochloraz, prochloraz-manganese,proclonol, procyazine, procymidone, prodiamine, profenofos, profluazol,profluralin, profluthrin, profoxydim, proglinazine, proglinazine-ethyl,prohexadione, prohexadione-calcium, prohydrojasmon, promacyl, promecarb,prometon, prometryn, promurit, propachlor, propamidine, propamidinedihydrochloride, propamocarb, propamocarb hydrochloride, propanil,propaphos, propaquizafop, propargite, proparthrin, propazine,propetamphos, propham, propiconazole, propineb, propisochlor, propoxur,propoxycarbazone, propoxycarbazone-sodium, propyl isome,propyrisulfuron, propyzamide, proquinazid, prosuler, prosulfalin,prosulfocarb, prosulfuron, prothidathion, prothiocarb, prothiocarbhydrochloride, prothioconazole, prothiofos, prothoate, protrifenbute,proxan, proxan-sodium, prynachlor, pydanon, pymetrozine, pyracarbolid,pyraclofos, pyraclonil, pyraclostrobin, pyraflufen, pyraflufen-ethyl,pyrafluprole, pyramat, pyrametostrobin, pyraoxystrobin, pyrasulfotole,pyrazolynate, pyrazophos, pyrazosulfuron, pyrazosulfuron-ethyl,pyrazothion, pyrazoxyfen, pyresmethrin, pyrethrin I, pyrethrin II,pyrethrins, pyribambenz-isopropyl, pyribambenz-propyl, pyribencarb,pyribenzoxim, pyributicarb, pyriclor, pyridaben, pyridafol, pyridalyl,pyridaphenthion, pyridate, pyridinitril, pyrifenox, pyrifluquinazon,pyriftalid, pyrimethanil, pyrimidifen, pyriminobac, pyriminobac-methyl,pyrimisulfan, pyrimitate, pyrinuron, pyriofenone, pyriprole,pyripropanol, pyriproxyfen, pyrithiobac, pyrithiobac-sodium, pyrolan,pyroquilon, pyroxasulfone, pyroxsulam, pyroxychlor, pyroxyfur, quassia,quinacetol, quinacetol sulfate, quinalphos, quinalphos-methyl,quinazamid, quinclorac, quinconazole, quinmerac, quinoclamine,quinonamid, quinothion, quinoxyfen, quintiofos, quintozene, quizalofop,quizalofop-ethyl, quizalofop-P, quizalofop-P-ethyl,quizalofop-P-tefuryl, quwenzhi, quyingding, rabenzazole, rafoxanide,rebemide, resmethrin, rhodethanil, rhodojaponin-III, ribavirin,rimsulfuron, rotenone, ryania, saflufenacil, saijunmao, saisentong,salicylanilide, sanguinarine, santonin, schradan, scilliroside,sebuthylazine, secbumeton, sedaxane, selamectin, semiamitraz,semiamitraz chloride, sesamex, sesamolin, sethoxydim, shuangjiaancaolin,siduron, siglure, silafluofen, silatrane, silica gel, silthiofam,simazine, simeconazole, simeton, simetryn, sintofen, SMA, S-metolachlor,sodium arsenite, sodium azide, sodium chlorate, sodium fluoride, sodiumfluoroacetate, sodium hexafluorosilicate, sodium naphthenate, sodiumorthophenylphenoxide, sodium pentachlorophenoxide, sodium polysulfide,sodium thiocyanate, sodium α-naphthaleneacetate, sophamide, spinetoram,spinosad, spirodiclofen, spiromesifen, spirotetramat, spiroxamine,streptomycin, streptomycin sesquisulfate, strychnine, sulcatol,sulcofuron, sulcofuron-sodium, sulcotrione, sulfallate, sulfentrazone,sulfuram, sulfluramid, sulfometuron, sulfometuron-methyl, sulfosulfuron,sulfotep, sulfoxaflor, sulfoxide, sulfoxime, sulfur, sulfuric acid,sulfuryl fluoride, sulglycapin, sulprofos, sultropen, swep,tau-fluvalinate, tavron, tazimcarb, TCA, TCA-ammonium, TCA-calcium,TCA-ethadyl, TCA-magnesium, TCA-sodium, TDE, tebuconazole, tebufenozide,tebufenpyrad, tebufloquin, tebupirimfos, tebutam, tebuthiuron,tecloftalam, tecnazene, tecoram, teflubenzuron, tefluthrin,tefuryltrione, tembotrione, temephos, tepa, TEPP, tepraloxydim,terallethrin, terbacil, terbucarb, terbuchlor, terbufos, terbumeton,terbuthylazine, terbutryn, tetcyclacis, tetrachloroethane,tetrachlorvinphos, tetraconazole, tetradifon, tetrafluoron,tetramethrin, tetramethylfluthrin, tetramine, tetranactin, tetrasul,thallium sulfate, thenylchlor, theta-cypermethrin, thiabendazole,thiacloprid, thiadifluor, thiamethoxam, thiapronil, thiazafluoron,thiazopyr, thicrofos, thicyofen, thidiazimin, thidiazuron,thiencarbazone, thiencarbazone-methyl, thifensulfuron,thifensulfuron-methyl, thifluzamide, thiobencarb, thiocarboxime,thiochlorfenphim, thiocyclam, thiocyclam hydrochloride, thiocyclamoxalate, thiodiazole-copper, thiodicarb, thiofanox, thiofluoximate,thiohempa, thiomersal, thiometon, thionazin, thiophanate,thiophanate-methyl, thioquinox, thiosemicarbazide, thiosultap,thiosultap-diammonium, thiosultap-disodium, thiosultap-monosodium,thiotepa, thiram, thuringiensin, tiadinil, tiaojiean, tiocarbazil,tioclorim, tioxymid, tirpate, tolclofos-methyl, tolfenpyrad,tolylfluanid, tolylmercury acetate, topramezone, tralkoxydim,tralocythrin, tralomethrin, tralopyril, transfluthrin, transpermethrin,tretamine, triacontanol, triadimefon, triadimenol, triafamone,tri-allate, triamiphos, triapenthenol, triarathene, triarimol,triasulfuron, triazamate, triazbutil, triaziflam, triazophos,triazoxide, tribenuron, tribenuron-methyl, tribufos, tributyltin oxide,tricamba, trichlamide, trichlorfon, trichlormetaphos-3, trichloronat,triclopyr, triclopyr-butotyl, triclopyr-ethyl,triclopyr-triethylammonium, tricyclazole, tridemorph, tridiphane,trietazine, trifenmorph, trifenofos, trifloxystrobin, trifloxysulfuron,trifloxysulfuron-sodium, triflumizole, triflumuron, trifluralin,triflusulfuron, triflusulfuron-methyl, trifop, trifop-methyl,trifopsime, triforine, trihydroxytriazine, trimedlure, trimethacarb,trimeturon, trinexapac, trinexapac-ethyl, triprene, tripropindan,triptolide, tritac, triticonazole, tritosulfuron, trunc-call,uniconazole, uniconazole-P, urbacide, uredepa, valerate, validamycin,valifenalate, valone, vamidothion, vangard, vaniliprole, vernolate,vinclozolin, warfarin, warfarin-potassium, warfarin-sodium,xiaochongliulin, xinjunan, xiwojunan, XMC, xylachlor, xylenols,xylylcarb, yishijing, zarilamid, zeatin, zengxiaoan, zeta-cypermethrin,zinc naphthenate, zinc phosphide, zinc thiazole, zineb, ziram,zolaprofos, zoxamide, zuomihuanglong, α-chlorohydrin, α-ecdysone,α-multistriatin, and α-naphthaleneacetic acid. For more informationconsult the “COMPENDIUM OF PESTICIDE COMMON NAMES” located athttp://www.alanwood.net/pesticides/index.html. Also consult “THEPESTICIDE MANUAL” 14th Edition, edited by C D S Tomlin, copyright 2006by British Crop Production Council, or its prior or more recenteditions.

Biopesticides

Molecules of Formula One may also be used in combination (such as in acompositional mixture, or a simultaneous or sequential application) withone or more biopesticides. The term “biopesticide” is used for microbialbiological pest control agents that are applied in a similar manner tochemical pesticides. Commonly these are bacterial, but there are alsoexamples of fungal control agents, including Trichoderma spp. andAmpelomyces quisqualis (a control agent for grape powdery mildew).Bacillus subtilis are used to control plant pathogens. Weeds and rodentshave also been controlled with microbial agents. One well-knowninsecticide example is Bacillus thuringiensis, a bacterial disease ofLepidoptera, Coleoptera, and Diptera. Because it has little effect onother organisms, it is considered more environmentally friendly thansynthetic pesticides. Biological insecticides include products based on:

1. entomopathogenic fungi (e.g. Metarhizium anisopliae);

2. entomopathogenic nematodes (e.g. Steinemema feltiae); and

3. entomopathogenic viruses (e.g. Cydia pomonella granulovirus).

Other examples of entomopathogenic organisms include, but are notlimited to, baculoviruses, bacteria and other prokaryotic organisms,fungi, protozoa and Microsproridia. Biologically derived insecticidesinclude, but not limited to, rotenone, veratridine, as well as microbialtoxins; insect tolerant or resistant plant varieties; and organismsmodified by recombinant DNA technology to either produce insecticides orto convey an insect resistant property to the genetically modifiedorganism. In one embodiment, the molecules of Formula One may be usedwith one or more biopesticides in the area of seed treatments and soilamendments. The Manual of Biocontrol Agents gives a review of theavailable biological insecticide (and other biology-based control)products. Copping L. G. (ed.) (2004). The Manual of Biocontrol Agents(formerly the Biopesticide Manual) 3rd Edition. British Crop ProductionCouncil (BCPC), Farnham, Surrey UK.

Other Active Compounds

Molecules of Formula One may also be used in combination (such as in acompositional mixture, or a simultaneous or sequential application) withone or more of the following:

-   1.    3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one;-   2.    3-(4′-chloro-2,4-dimethyl[1,1′-biphenyl]-3-yl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one;-   3. 4-[[(6-chloro-3-pyridinyl)methyl]methylamino]-2(5H)-furanone;-   4.    4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5H)-furanone;-   5.    3-chloro-N2-[(1S)-1-methyl-2-(methylsulfonyl)ethyl]-N1-[2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]-1,2-benzenedicarboxamide;-   6. 2-cyano-N-ethyl-4-fluoro-3-methoxy-benenesulfonamide;-   7. 2-cyano-N-ethyl-3-methoxy-benzenesulfonamide;-   8. 2-cyano-3-difluoromethoxy-N-ethyl-4-fluoro-benzenesulfonamide;-   9. 2-cyano-3-fluoromethoxy-N-ethyl-benzenesulfonamide;-   10. 2-cyano-6-fluoro-3-methoxy-N,N-dimethyl-benzenesulfonamide;-   11. 2-cyano-N-ethyl-6-fluoro-3-methoxy-N-methyl-benzenesulfonamide;-   12. 2-cyano-3-difluoromethoxy-N,N-dimethylbenzenesulfon-amide;-   13.    3-(difluoromethyl)-N-[2-(3,3-dimethylbutyl)phenyl]-1-methyl-1H-pyrazole-4-carboxamide;-   14.    N-ethyl-2,2-dimethylpropionamide-2-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)    hydrazone;-   15.    N-ethyl-2,2-dichloro-1-methylcyclopropane-carboxamide-2-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)    hydrazone nicotine;-   16.    O-{(E-)-[2-(4-chloro-phenyl)-2-cyano-1-(2-trifluoromethylphenyl)-vinyl]}S-methyl    thiocarbonate;-   17.    (E)-N1-[(2-chloro-1,3-thiazol-5-ylmethyl)]-N2-cyano-N1-methylacetamidine;-   18.    1-(6-chloropyridin-3-ylmethyl)-7-methyl-8-nitro-1,2,3,5,6,7-hexahydro-imidazo[1,2-a]pyridin-5-ol;-   19. 4-[4-chlorophenyl-(2-butylidine-hydrazono)methyl)]phenyl    mesylate; and-   20.    N-Ethyl-2,2-dichloro-1-methylcyclopropanecarboxamide-2-(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyl)hydrazone.

Synergistic Mixtures

Molecules of Formula One may be used with certain active compounds toform synergistic mixtures where the mode of action of such compoundscompared to the mode of action of the molecules of Formula One are thesame, similar, or different. Examples of modes of action include, butare not limited to: acetylcholinesterase inhibitor; sodium channelmodulator; chitin biosynthesis inhibitor; GABA and glutamate-gatedchloride channel antagonist; GABA and glutamate-gated chloride channelagonist; acetylcholine receptor agonist; acetylcholine receptorantagonist; MET I inhibitor; Mg-stimulated ATPase inhibitor; nicotinicacetylcholine receptor; Midgut membrane disrupter; oxidativephosphorylation disrupter, and ryanodine receptor (RyRs). Generally,weight ratios of the molecules of Formula One in a synergistic mixturewith another compound are from about 10:1 to about 1:10, in anotherembodiment from about 5:1 to about 1:5, and in another embodiment fromabout 3:1, and in another embodiment about 1:1.

Formulations

A pesticide is rarely suitable for application in its pure form. It isusually necessary to add other substances so that the pesticide can beused at the required concentration and in an appropriate form,permitting ease of application, handling, transportation, storage, andmaximum pesticide activity. Thus, pesticides are formulated into, forexample, baits, concentrated emulsions, dusts, emulsifiableconcentrates, fumigants, gels, granules, microencapsulations, seedtreatments, suspension concentrates, suspoemulsions, tablets, watersoluble liquids, water dispersible granules or dry flowables, wettablepowders, and ultra-low volume solutions. For further information onformulation types see “Catalogue of Pesticide Formulation Types andInternational Coding System” Technical Monograph no 2, 5th Edition byCropLife International (2002).

Pesticides are applied most often as aqueous suspensions or emulsionsprepared from concentrated formulations of such pesticides. Suchwater-soluble, water-suspendable, or emulsifiable formulations areeither solids, usually known as wettable powders, or water dispersiblegranules, or liquids usually known as emulsifiable concentrates, oraqueous suspensions. Wettable powders, which may be compacted to formwater dispersible granules, comprise an intimate mixture of thepesticide, a carrier, and surfactants. The concentration of thepesticide is usually from about 10% to about 90% by weight. The carrieris usually selected from among the attapulgite clays, themontmorillonite clays, the diatomaceous earths, or the purifiedsilicates. Effective surfactants, comprising from about 0.5% to about10% of the wettable powder, are found among sulfonated lignins,condensed naphthalenesulfonates, naphthalenesulfonates,alkylbenzenesulfonates, alkyl sulfates, and non-ionic surfactants suchas ethylene oxide adducts of alkyl phenols.

Emulsifiable concentrates of pesticides comprise a convenientconcentration of a pesticide, such as from about 50 to about 500 gramsper liter of liquid dissolved in a carrier that is either a watermiscible solvent or a mixture of water-immiscible organic solvent andemulsifiers. Useful organic solvents include aromatics, especiallyxylenes and petroleum fractions, especially the high-boilingnaphthalenic and olefinic portions of petroleum such as heavy aromaticnaphtha. Other organic solvents may also be used, such as the terpenicsolvents including rosin derivatives, aliphatic ketones such ascyclohexanone, and complex alcohols such as 2-ethoxyethanol. Suitableemulsifiers for emulsifiable concentrates are selected from conventionalanionic and non-ionic surfactants.

Aqueous suspensions comprise suspensions of water-insoluble pesticidesdispersed in an aqueous carrier at a concentration in the range fromabout 5% to about 50% by weight. Suspensions are prepared by finelygrinding the pesticide and vigorously mixing it into a carrier comprisedof water and surfactants. Ingredients, such as inorganic salts andsynthetic or natural gums may also be added, to increase the density andviscosity of the aqueous carrier. It is often most effective to grindand mix the pesticide at the same time by preparing the aqueous mixtureand homogenizing it in an implement such as a sand mill, ball mill, orpiston-type homogenizer.

Pesticides may also be applied as granular compositions that areparticularly useful for applications to the soil. Granular compositionsusually contain from about 0.5% to about 10% by weight of the pesticide,dispersed in a carrier that comprises clay or a similar substance. Suchcompositions are usually prepared by dissolving the pesticide in asuitable solvent and applying it to a granular carrier which has beenpre-formed to the appropriate particle size, in the range of from about0.5 to about 3 mm. Such compositions may also be formulated by making adough or paste of the carrier and compound and crushing and drying toobtain the desired granular particle size.

Dusts containing a pesticide are prepared by intimately mixing thepesticide in powdered form with a suitable dusty agricultural carrier,such as kaolin clay, ground volcanic rock, and the like. Dusts cansuitably contain from about 1% to about 10% of the pesticide. They canbe applied as a seed dressing or as a foliage application with a dustblower machine.

It is equally practical to apply a pesticide in the form of a solutionin an appropriate organic solvent, usually petroleum oil, such as thespray oils, which are widely used in agricultural chemistry.

Pesticides can also be applied in the form of an aerosol composition. Insuch compositions the pesticide is dissolved or dispersed in a carrier,which is a pressure-generating propellant mixture. The aerosolcomposition is packaged in a container from which the mixture isdispensed through an atomizing valve.

Pesticide baits are formed when the pesticide is mixed with food or anattractant or both. When the pests eat the bait they also consume thepesticide. Baits may take the form of granules, gels, flowable powders,liquids, or solids. They can be used in pest harborages.

Fumigants are pesticides that have a relatively high vapor pressure andhence can exist as a gas in sufficient concentrations to kill pests insoil or enclosed spaces. The toxicity of the fumigant is proportional toits concentration and the exposure time. They are characterized by agood capacity for diffusion and act by penetrating the pest'srespiratory system or being absorbed through the pest's cuticle.Fumigants are applied to control stored product pests under gas proofsheets, in gas sealed rooms or buildings or in special chambers.

Pesticides can be microencapsulated by suspending the pesticideparticles or droplets in plastic polymers of various types. By alteringthe chemistry of the polymer or by changing factors in the processing,microcapsules can be formed of various sizes, solubility, wallthicknesses, and degrees of penetrability. These factors govern thespeed with which the active ingredient within is released, which inturn, affects the residual performance, speed of action, and odor of theproduct.

Oil solution concentrates are made by dissolving pesticide in a solventthat will hold the pesticide in solution. Oil solutions of a pesticideusually provide faster knockdown and kill of pests than otherformulations due to the solvents themselves having pesticidal action andthe dissolution of the waxy covering of the integument increasing thespeed of uptake of the pesticide. Other advantages of oil solutionsinclude better storage stability, better penetration of crevices, andbetter adhesion to greasy surfaces.

Another embodiment is an oil-in-water emulsion, wherein the emulsioncomprises oily globules which are each provided with a lamellar liquidcrystal coating and are dispersed in an aqueous phase, wherein each oilyglobule comprises at least one compound which is agriculturally active,and is individually coated with a monolamellar or oligolamellar layercomprising: (1) at least one non-ionic lipophilic surface-active agent,(2) at least one non-ionic hydrophilic surface-active agent and (3) atleast one ionic surface-active agent, wherein the globules having a meanparticle diameter of less than 800 nanometers. Further information onthe embodiment is disclosed in U.S. patent publication 20070027034published Feb. 1, 2007, having patent application Ser. No. 11/495,228.For ease of use, this embodiment will be referred to as “OIWE”.

For further information consult “Insect Pest Management” 2nd Edition byD. Dent, copyright CAB International (2000). Additionally, for moredetailed information consult “Handbook of Pest Control—The Behavior,Life History, and Control of Household Pests” by Arnold Mallis, 9thEdition, copyright 2004 by GIE Media Inc.

Other Formulation Components

Generally, when the molecules disclosed in Formula One are used in aformulation, such formulation can also contain other components. Thesecomponents include, but are not limited to, (this is a non-exhaustiveand non-mutually exclusive list) wetters, spreaders, stickers,penetrants, buffers, sequestering agents, drift reduction agents,compatibility agents, anti-foam agents, cleaning agents, andemulsifiers. A few components are described forthwith.

A wetting agent is a substance that when added to a liquid increases thespreading or penetration power of the liquid by reducing the interfacialtension between the liquid and the surface on which it is spreading.Wetting agents are used for two main functions in agrochemicalformulations: during processing and manufacture to increase the rate ofwetting of powders in water to make concentrates for soluble liquids orsuspension concentrates; and during mixing of a product with water in aspray tank to reduce the wetting time of wettable powders and to improvethe penetration of water into water-dispersible granules. Examples ofwetting agents used in wettable powder, suspension concentrate, andwater-dispersible granule formulations are: sodium lauryl sulfate;sodium dioctyl sulfosuccinate; alkyl phenol ethoxylates; and aliphaticalcohol ethoxylates.

A dispersing agent is a substance which adsorbs onto the surface ofparticles and helps to preserve the state of dispersion of the particlesand prevents them from reaggregating. Dispersing agents are added toagrochemical formulations to facilitate dispersion and suspension duringmanufacture, and to ensure the particles redisperse into water in aspray tank. They are widely used in wettable powders, suspensionconcentrates and water-dispersible granules. Surfactants that are usedas dispersing agents have the ability to adsorb strongly onto a particlesurface and provide a charged or steric barrier to reaggregation ofparticles. The most commonly used surfactants are anionic, non-ionic, ormixtures of the two types. For wettable powder formulations, the mostcommon dispersing agents are sodium lignosulfonates. For suspensionconcentrates, very good adsorption and stabilization are obtained usingpolyelectrolytes, such as sodium naphthalene sulfonate formaldehydecondensates. Tristyrylphenol ethoxylate phosphate esters are also used.Non-ionics such as alkylarylethylene oxide condensates and EO-PO blockcopolymers are sometimes combined with anionics as dispersing agents forsuspension concentrates. In recent years, new types of very highmolecular weight polymeric surfactants have been developed as dispersingagents. These have very long hydrophobic ‘backbones’ and a large numberof ethylene oxide chains forming the ‘teeth’ of a ‘comb’ surfactant.These high molecular weight polymers can give very good long-termstability to suspension concentrates because the hydrophobic backboneshave many anchoring points onto the particle surfaces. Examples ofdispersing agents used in agrochemical formulations are: sodiumlignosulfonates; sodium naphthalene sulfonate formaldehyde condensates;tristyrylphenol ethoxylate phosphate esters; aliphatic alcoholethoxylates; alkyl ethoxylates; EO-PO block copolymers; and graftcopolymers.

An emulsifying agent is a substance which stabilizes a suspension ofdroplets of one liquid phase in another liquid phase. Without theemulsifying agent the two liquids would separate into two immiscibleliquid phases. The most commonly used emulsifier blends containalkylphenol or aliphatic alcohol with twelve or more ethylene oxideunits and the oil-soluble calcium salt of dodecylbenzenesulfonic acid. Arange of hydrophile-lipophile balance (“HLB”) values from 8 to 18 willnormally provide good stable emulsions. Emulsion stability can sometimesbe improved by the addition of a small amount of an EO-PO blockcopolymer surfactant.

A solubilizing agent is a surfactant which will form micelles in waterat concentrations above the critical micelle concentration. The micellesare then able to dissolve or solubilize water-insoluble materials insidethe hydrophobic part of the micelle. The types of surfactants usuallyused for solubilization are non-ionics, sorbitan monooleates, sorbitanmonooleate ethoxylates, and methyl oleate esters.

Surfactants are sometimes used, either alone or with other additivessuch as mineral or vegetable oils as adjuvants to spray-tank mixes toimprove the biological performance of the pesticide on the target. Thetypes of surfactants used for bioenhancement depend generally on thenature and mode of action of the pesticide. However, they are oftennon-ionics such as: alkyl ethoxylates; linear aliphatic alcoholethoxylates; aliphatic amine ethoxylates.

A carrier or diluent in an agricultural formulation is a material addedto the pesticide to give a product of the required strength. Carriersare usually materials with high absorptive capacities, while diluentsare usually materials with low absorptive capacities. Carriers anddiluents are used in the formulation of dusts, wettable powders,granules and water-dispersible granules.

Organic solvents are used mainly in the formulation of emulsifiableconcentrates, oil-in-water emulsions, suspoemulsions, and ultra-lowvolume formulations, and to a lesser extent, granular formulations.Sometimes mixtures of solvents are used. The first main groups ofsolvents are aliphatic paraffinic oils such as kerosene or refinedparaffins. The second main group (and the most common) comprises thearomatic solvents such as xylene and higher molecular weight fractionsof C9 and C10 aromatic solvents. Chlorinated hydrocarbons are useful ascosolvents to prevent crystallization of pesticides when the formulationis emulsified into water. Alcohols are sometimes used as cosolvents toincrease solvent power. Other solvents may include vegetable oils, seedoils, and esters of vegetable and seed oils.

Thickeners or gelling agents are used mainly in the formulation ofsuspension concentrates, emulsions and suspoemulsions to modify therheology or flow properties of the liquid and to prevent separation andsettling of the dispersed particles or droplets. Thickening, gelling,and anti-settling agents generally fall into two categories, namelywater-insoluble particulates and water-soluble polymers. It is possibleto produce suspension concentrate formulations using clays and silicas.Examples of these types of materials, include, but are not limited to,montmorillonite, bentonite, magnesium aluminum silicate, andattapulgite. Water-soluble polysaccharides have been used asthickening-gelling agents for many years. The types of polysaccharidesmost commonly used are natural extracts of seeds and seaweeds or aresynthetic derivatives of cellulose. Examples of these types of materialsinclude, but are not limited to, guar gum; locust bean gum; carrageenam;alginates; methyl cellulose; sodium carboxymethyl cellulose (SCMC);hydroxyethyl cellulose (HEC). Other types of anti-settling agents arebased on modified starches, polyacrylates, polyvinyl alcohol andpolyethylene oxide. Another good anti-settling agent is xanthan gum.

Microorganisms can cause spoilage of formulated products. Thereforepreservation agents are used to eliminate or reduce their effect.Examples of such agents include, but are not limited to: propionic acidand its sodium salt; sorbic acid and its sodium or potassium salts;benzoic acid and its sodium salt; p-hydroxybenzoic acid sodium salt;methyl p-hydroxybenzoate; and 1,2-benzisothiazolin-3-one (BIT).

The presence of surfactants often causes water-based formulations tofoam during mixing operations in production and in application through aspray tank. In order to reduce the tendency to foam, anti-foam agentsare often added either during the production stage or before fillinginto bottles. Generally, there are two types of anti-foam agents, namelysilicones and non-silicones. Silicones are usually aqueous emulsions ofdimethyl polysiloxane, while the non-silicone anti-foam agents arewater-insoluble oils, such as octanol and nonanol, or silica. In bothcases, the function of the anti-foam agent is to displace the surfactantfrom the air-water interface.

“Green” agents (e.g., adjuvants, surfactants, solvents) can reduce theoverall environmental footprint of crop protection formulations. Greenagents are biodegradable and generally derived from natural and/orsustainable sources, e.g. plant and animal sources. Specific examplesare: vegetable oils, seed oils, and esters thereof, also alkoxylatedalkyl polyglucosides.

For further information, see “Chemistry and Technology of AgrochemicalFormulations” edited by D. A. Knowles, copyright 1998 by Kluwer AcademicPublishers. Also see “Insecticides in Agriculture andEnvironment—Retrospects and Prospects” by A. S. Perry, I. Yamamoto, I.Ishaaya, and R. Perry, copyright 1998 by Springer-Verlag.

Pests

In general, the molecules of Formula One may be used to control pestse.g. beetles, earwigs, cockroaches, flies. aphids, scales, whiteflies,leafhoppers, ants, wasps, termites, moths, butterflies, lice,grasshoppers, locusts, crickets, fleas, thrips, bristletails, mites,ticks, nematodes, and symphylans.

In another embodiment, the molecules of Formula One may be used tocontrol pests in the Phyla Nematoda and/or Arthropoda.

In another embodiment, the molecules of Formula One may be used tocontrol pests in the Subphyla Chelicerata, Myriapoda, and/or Hexapoda.

In another embodiment, the molecules of Formula One may be used tocontrol pests in the Classes of Arachnida, Symphyla, and/or Insecta.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Anoplura. A non-exhaustive list of particulargenera includes, but is not limited to, Haematopinus spp., Hoplopleuraspp., Linognathus spp., Pediculus spp., and Polyplax spp. Anon-exhaustive list of particular species includes, but is not limitedto, Haematopinus asini, Haematopinus suis, Linognathus setosus,Linognathus ovillus, Pediculus humanus capitis, Pediculus humanushumanus, and Pthirus pubis.

In another embodiment, the molecules of Formula One may be used tocontrol pests in the Order Coleoptera. A non-exhaustive list ofparticular genera includes, but is not limited to, Acanthoscelides spp.,Agriotes spp., Anthonomus spp., Apion spp., Apogonia spp., Aulacophoraspp., Bruchus spp., Cerosterna spp., Cerotoma spp., Ceutorhynchus spp.,Chaetocnema spp., Colaspis spp., Ctenicera spp., Curculio spp.,Cyclocephala spp., Diabrotica spp., Hypera spp., Ips spp., Lyctus spp.,Megascelis spp., Meligethes spp., Otiorhynchus spp., Pantomorus spp.,Phyllophaga spp., Phyllotreta spp., Rhizotrogus spp., Rhynchites spp.,Rhynchophorus spp., Scolytus spp., Sphenophorus spp., Sitophilus spp.,and Tribolium spp. A non-exhaustive list of particular species includes,but is not limited to, Acanthoscelides obtectus, Agrilus planipennis,Anoplophora glabripennis, Anthonomus grandis, Ataenius spretulus,Atomaria linearis, Bothynoderes punctiventris, Bruchus pisorum,Callosobruchus maculatus, Carpophilus hemipterus, Cassida vittata,Cerotoma trifurcata, Ceutorhynchus assimilis, Ceutorhynchus napi,Conoderus scalaris, Conoderus stigmosus, Conotrachelus nenuphar, Cotinisnitida, Crioceris asparagi, Cryptolestes ferrugineus, Cryptolestespusillus, Cryptolestes turcicus, Cylindrocopturus adspersus, Deporausmarginatus, Dermestes lardarius, Dermestes maculatus, Epilachnavarivestis, Faustinus cubae, Hylobius pales, Hypera postica,Hypothenemus hampei, Lasioderma serricorne, Leptinotarsa decemlineata,Liogenys fiiscus, Liogenys suturalis, Lissorhoptrus oryzophilus,Maecolaspis joliveti, Melanotus communis, Meligethes aeneus, Melolonthamelolontha, Oberea brevis, Oberea linearis, Oryctes rhinoceros,Oryzaephilus mercator, Oryzaephilus surinamensis, Oulema melanopus,Oulema oryzae, Phyllophaga cuyabana, Popillia japonica, Prostephanustruncatus, Rhyzopertha dominica, Sitona lineatus, Sitophilus granarius,Sitophilus oryzae, Sitophilus zeamais, Stegobium paniceum, Triboliumcastaneum, Tribolium confusum, Trogoderma variabile, and Zabrustenebrioides.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Dermaptera.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Blattaria. A non-exhaustive list ofparticular species includes, but is not limited to, Blattella germanica,Blatta orientalis, Parcoblatta pennsylvanica, Periplaneta americana,Periplaneta australasiae, Periplaneta brunnea, Periplaneta fuliginosa,Pycnoscelus surinamensis, and Supella longipalpa.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Diptera. A non-exhaustive list of particulargenera includes, but is not limited to, Aedes spp., Agromyza spp.,Anastrepha spp., Anopheles spp., Bactrocera spp., Ceratitis spp.,Chrysops spp., Cochliomyia spp., Contarinia spp., Culex spp., Dasineuraspp., Delia spp., Drosophila spp., Fannia spp., Hylemyia spp., Liriomyzaspp., Musca spp., Phorbia spp., Tabanus spp., and Tipula spp. Anon-exhaustive list of particular species includes, but is not limitedto, Agromyza frontella, Anastrepha suspensa, Anastrepha ludens,Anastrepha obliqa, Bactrocera cucurbitae, Bactrocera dorsalis,Bactrocera invadens, Bactrocera zonata, Ceratitis capitata, Dasineurabrassicae, Delia platura, Fannia canicularis, Fannia scalaris,Gasterophilus intestinalis, Gracillia perseae, Haematobia irritans,Hypoderma lineatum, Liriomyza brassicae, Melophagus ovinus, Muscaautumnalis, Musca domestica, Oestrus ovis, Oscinella frit, Pegomyabetae, Psila rosae, Rhagoletis cerasi, Rhagoletis pomonella, Rhagoletismendax, Sitodiplosis mosellana, and Stomoxys calcitrans.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Hemiptera. A non-exhaustive list ofparticular genera includes, but is not limited to, Adelges spp.,Aulacaspis spp., Aphrophora spp., Aphis spp., Bemisia spp., Ceroplastesspp., Chionaspis spp., Chrysomphalus spp., Coccus spp., Empoasca spp.,Lepidosaphes spp., Lagynotomus spp., Lygus spp., Macrosiphum spp.,Nephotettix spp., Nezara spp., Philaenus spp., Phytocoris spp.,Piezodorus spp., Planococcus spp., Pseudococcus spp., Rhopalosiphumspp., Saissetia spp., Therioaphis spp., Toumeyella spp., Toxoptera spp.,Trialeurodes spp., Triatoma spp. and Unaspis spp. A non-exhaustive listof particular species includes, but is not limited to, Acrosternumhilare, Acyrthosiphon pisum, Aleyrodes proletella, Aleurodicusdispersus, Aleurothrixus floccosus, Amrasca biguttula biguttula,Aonidiella aurantii, Aphis gossypii, Aphis glycines, Aphis pomi,Aulacorthum solani, Bemisia argentifolii, Bemisia tabaci, Blissusleucopterus, Brachycorynella asparagi, Brevennia rehi, Brevicorynebrassicae, Calocoris norvegicus, Ceroplastes rubens, Cimex hemipterus,Cimex lectularius, Dagbertus fasciatus, Dichelops furcatus, Diuraphisnoxia, Diaphorina citri, Dysaphis plantaginea, Dysdercus suturellus,Edessa meditabunda, Eriosoma lanigerum, Eurygaster maura, Euschistusheros, Euschistus servus, Helopeltis antonii, Helopeltis theivora,Icerya purchasi, Idioscopus nitidulus, Laodelphax striatellus,Leptocorisa oratorius, Leptocorisa varicornis, Lygus hesperus,Maconellicoccus hirsutus, Macrosiphum euphorbiae, Macrosiphum granarium,Macrosiphum rosae, Macrosteles quadrilineatus, Mahanarva frimbiolata,Metopolophium dirhodum, Mictis longicornis, Myzus persicae, Nephotettixcinctipes, Neurocolpus longirostris, Nezara viridula, Nilaparvatalugens, Parlatoria pergandii, Parlatoria ziziphi, Peregrinus maidis,Phylloxera vitifoliae, Physokermes piceae, Phytocoris californicus,Phytocoris relativus, Piezodorus guildinii, Poecilocapsus lineatus,Psallus vaccinicola, Pseudacysta perseae, Pseudococcus brevipes,Quadraspidiotus perniciosus, Rhopalosiphum maidis, Rhopalosiphum padi,Saissetia oleae, Scaptocoris castanea, Schizaphis graminum, Sitobionavenae, Sogatella furcifera, Trialeurodes vaporariorum, Trialeurodesabutiloneus, Unaspis yanonensis, and Zulia entrerriana.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Hymenoptera. A non-exhaustive list ofparticular genera includes, but is not limited to, Acromyrmex spp., Attaspp., Camponotus spp., Diprion spp., Formica spp., Monomorium spp.,Neodiprion spp., Pogonomyrmex spp., Polistes spp., Solenopsis spp.,Vespula spp., and Xylocopa spp. A non-exhaustive list of particularspecies includes, but is not limited to, Athalia rosae, Atta texana,Iridomyrmex humilis, Monomorium minimum, Monomorium pharaonis,Solenopsis invicta, Solenopsis geminata, Solenopsis molesta, Solenopsisrichtery, Solenopsis xyloni, and Tapinoma sessile.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Isoptera. A non-exhaustive list of particulargenera includes, but is not limited to, Coptotermes spp., Cornitermesspp., Cryptotermes spp., Heterotermes spp., Kalotermes spp.,Incisitermes spp., Macrotermes spp., Marginitermes spp., Microcerotermesspp., Procornitermes spp., Reticulitermes spp., Schedorhinotermes spp.,and Zootermopsis spp. A non-exhaustive list of particular speciesincludes, but is not limited to, Coptotermes curvignathus, Coptotermesfrenchi, Coptotermes formosanus, Heterotermes aureus, Microtermes obesi,Reticulitermes banyulensis, Reticulitermes grassei, Reticulitermesflavipes, Reticulitermes hageni, Reticulitermes hesperus, Reticulitermessantonensis, Reticulitermes speratus, Reticulitermes tibialis, andReticulitermes virginicus.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Lepidoptera. A non-exhaustive list ofparticular genera includes, but is not limited to, Adoxophyes spp.,Agrotis spp., Argyrotaenia spp., Cacoecia spp., Caloptilia spp., Chilospp., Chrysodeixis spp., Colias spp., Crambus spp., Diaphania spp.,Diatraea spp., Earias spp., Ephestia spp., Epimecis spp., Feltia spp.,Gortyna spp., Helicoverpa spp., Heliothis spp., Indarbela spp.,Lithocolletis spp., Loxagrotis spp., Malacosoma spp., Peridroma spp.,Phyllonorycter spp., Pseudaletia spp., Sesamia spp., Spodoptera spp.,Synanthedon spp., and Yponomeuta spp. A non-exhaustive list ofparticular species includes, but is not limited to, Achaea janata,Adoxophyes orana, Agrotis ipsilon, Alabama argillacea, Amorbia cuneana,Amyelois transitella, Anacamptodes defectaria, Anarsia lineatella,Anomis sabulifera, Anticarsia gemmatalis, Archips argyrospila, Archipsrosana, Argyrotaenia citrana, Autographa gamma, Bonagota cranaodes,Borbo cinnara, Bucculatrix thurberiella, Capua reticulana, Carposinaniponensis, Chlumetia transversa, Choristoneura rosaceana,Cnaphalocrocis medinalis, Conopomorpha cramerella, Cossus cossus, Cydiacaryana, Cydia funebrana, Cydia molesta, Cydia nigricana, Cydiapomonella, Darna diducta, Diatraea saccharalis, Diatraea grandiosella,Earias insulana, Earias vittella, Ecdytolopha aurantianum, Elasmopalpuslignosellus, Ephestia cautella, Ephestia elutella, Ephestia kuehniella,Epinotia aporema, Epiphyas postvittana, Erionota thrax, Eupoeciliaambiguella, Euxoa auxiliaris, Grapholita molesta, Hedylepta indicata,Helicoverpa armigera, Helicoverpa zea, Heliothis virescens, Hellulaundalis, Keiferia lycopersicella, Leucinodes orbonalis, Leucopteracoffeella, Leucoptera malifoliella, Lobesia botrana, Loxagrotisalbicosta, Lymantria dispar, Lyonetia clerkella, Mahasena corbetti,Mamestra brassicae, Maruca testulalis, Metisa plana, Mythimna unipuncta,Neoleucinodes elegantalis, Nymphula depunctalis, Operophtera brumata,Ostrinia nubilalis, Oxydia vesulia, Pandemis cerasana, Pandemisheparana, Papilio demodocus, Pectinophora gossypiella, Peridroma saucia,Perileucoptera coffeella, Phthorimaea operculella, Phyllocnistiscitrella, Pieris rapae, Plathypena scabra, Plodia interpunctella,Plutella xylostella, Polychrosis viteana, Prays endocarpa, Prays oleae,Pseudaletia unipuncta, Pseudoplusia includens, Rachiplusia nu,Scirpophaga incertulas, Sesamia inferens, Sesamia nonagrioides, Setoranitens, Sitotroga cerealella, Sparganothis pilleriana, Spodopteraexigua, Spodoptera frugiperda, Spodoptera eridania, Thecla basilides,Tineola bisselliella, Trichoplusia ni, Tuta absoluta, Zeuzera coffeae,and Zeuzera pyrina.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Mallophaga. A non-exhaustive list ofparticular genera includes, but is not limited to, Anaticola spp.,Bovicola spp., Chelopistes spp., Goniodes spp., Menacanthus spp., andTrichodectes spp. A non-exhaustive list of particular species includes,but is not limited to, Bovicola bovis, Bovicola caprae, Bovicola ovis,Chelopistes meleagridis, Goniodes dissimilis, Goniodes gigas,Menacanthus stramineus, Menopon gallinae, and Trichodectes canis.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Orthoptera. A non-exhaustive list ofparticular genera includes, but is not limited to, Melanoplus spp., andPterophylla spp. A non-exhaustive list of particular species includes,but is not limited to, Anabrus simplex, Gryllotalpa africana,Gryllotalpa australis, Gryllotalpa brachyptera, Gryllotalpa hexadactyla,Locusta migratoria, Microcentrum retinerve, Schistocerca gregaria, andScudderia furcata.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Siphonaptera. A non-exhaustive list ofparticular species includes, but is not limited to, Ceratophyllusgallinae, Ceratophyllus niger, Ctenocephalides canis, Ctenocephalidesfelis, and Pulex irritans.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Thysanoptera. A non-exhaustive list ofparticular genera includes, but is not limited to, Caliothrips spp.,Frankliniella spp., Scirtothrips spp., and Thrips spp. A non-exhaustivelist of particular sp. includes, but is not limited to, Frankliniellafusca, Frankliniella occidentalis, Frankliniella schultzei,Frankliniella williamsi, Heliothrips haemorrhoidalis, Rhipiphorothripscruentatus, Scirtothrips citri, Scirtothrips dorsalis, and Taeniothripsrhopalantennalis, Thrips hawaiiensis, Thrips nigropilosus, Thripsorientalis, Thrips tabaci.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Thysanura. A non-exhaustive list ofparticular genera includes, but is not limited to, Lepisma spp. andThermobia spp.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Acarina. A non-exhaustive list of particulargenera includes, but is not limited to, Acarus spp., Aculops spp.,Boophilus spp., Demodex spp., Dermacentor spp., Epitrimerus spp.,Eriophyes spp., Ixodes spp., Oligonychus spp., Panonychus spp.,Rhizoglyphus spp., and Tetranychus spp. A non-exhaustive list ofparticular species includes, but is not limited to, Acarapis woodi,Acarus siro, Aceria mangiferae, Aculops lycopersici, Aculus pelekassi,Aculus schlechtendali, Amblyomma americanum, Brevipalpus obovatus,Brevipalpus phoenicis, Dermacentor variabilis, Dermatophagoidespteronyssinus, Eotetranychus carpini, Notoedres cati, Oligonychuscoffeae, Oligonychus ilicis, Panonychus citri, Panonychus ulmi,Phyllocoptruta oleivora, Polyphagotarsonemus latus, Rhipicephalussanguineus, Sarcoptes scabiei, Tegolophus perseaflorae, Tetranychusurticae, and Varroa destructor.

In another embodiment, the molecules of Formula One may be used tocontrol pest of the Order Symphyla. A non-exhaustive list of particularsp. includes, but is not limited to, Scutigerella immaculata.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Phylum Nematoda. A non-exhaustive list ofparticular genera includes, but is not limited to, Aphelenchoides spp.,Belonolaimus spp., Criconemella spp., Ditylenchus spp., Heterodera spp.,Hirschmanniella spp., Hoplolaimus spp., Meloidogyne spp., Pratylenchusspp., and Radopholus spp. A non-exhaustive list of particular sp.includes, but is not limited to, Dirofilaria immitis, Heterodera zeae,Meloidogyne incognita, Meloidogyne javanica, Onchocerca volvulus,Radopholus similis, and Rotylenchulus reniformis.

For additional information consult “HANDBOOK OF PEST CONTROL—THEBEHAVIOR, LIFE HISTORY, AND CONTROL OF HOUSEHOLD PESTS” by ArnoldMallis, 9th Edition, copyright 2004 by GIE Media Inc.

Applications

Molecules of Formula One are generally used in amounts from about 0.01grams per hectare to about 5000 grams per hectare to provide control.Amounts from about 0.1 grams per hectare to about 500 grams per hectareare generally preferred, and amounts from about 1 gram per hectare toabout 50 grams per hectare are generally more preferred.

The area to which a molecule of Formula One is applied can be any areainhabited (or maybe inhabited, or traversed by) a pest, for example:where crops, trees, fruits, cereals, fodder species, vines, turf andornamental plants, are growing; where domesticated animals are residing;the interior or exterior surfaces of buildings (such as places wheregrains are stored), the materials of construction used in building (suchas impregnated wood), and the soil around buildings. Particular cropareas to use a molecule of Formula One include areas where apples, corn,sunflowers, cotton, soybeans, canola, wheat, rice, sorghum, barley,oats, potatoes, oranges, alfalfa, lettuce, strawberries, tomatoes,peppers, crucifers, pears, tobacco, almonds, sugar beets, beans andother valuable crops are growing or the seeds thereof are going to beplanted. It is also advantageous to use ammonium sulfate with a moleculeof Formula One when growing various plants.

Controlling pests generally means that pest populations, pest activity,or both, are reduced in an area. This can come about when: pestpopulations are repulsed from an area; when pests are incapacitated inor around an area; or pests are exterminated, in whole, or in part, inor around an area. Of course, a combination of these results can occur.Generally, pest populations, activity, or both are desirably reducedmore than fifty percent, preferably more than 90 percent. Generally, thearea is not in or on a human; consequently, the locus is generally anon-human area.

The molecules of Formula One may be used in mixtures, appliedsimultaneously or sequentially, alone or with other compounds to enhanceplant vigor (e.g. to grow a better root system, to better withstandstressful growing conditions). Such other compounds are, for example,compounds that modulate plant ethylene receptors, most notably1-methylcyclopropene (also known as 1-MCP). Furthermore, such moleculesmay be used during times when pest activity is low, such as before theplants that are growing begin to produce valuable agriculturalcommodities. Such times include the early planting season when pestpressure is usually low.

The molecules of Formula One can be applied to the foliar and fruitingportions of plants to control pests. The molecules will either come indirect contact with the pest, or the pest will consume the pesticidewhen eating leaf, fruit mass, or extracting sap, that contains thepesticide. The molecules of Formula One can also be applied to the soil,and when applied in this manner, root and stem feeding pests can becontrolled. The roots can absorb a molecule taking it up into the foliarportions of the plant to control above ground chewing and sap feedingpests.

Generally, with baits, the baits are placed in the ground where, forexample, termites can come into contact with, and/or be attracted to,the bait. Baits can also be applied to a surface of a building,(horizontal, vertical, or slant surface) where, for example, ants,termites, cockroaches, and flies, can come into contact with, and/or beattracted to, the bait. Baits can comprise a molecule of Formula One.

The molecules of Formula One can be encapsulated inside, or placed onthe surface of a capsule. The size of the capsules can range fromnanometer size (about 100-900 nanometers in diameter) to micrometer size(about 10-900 microns in diameter).

Because of the unique ability of the eggs of some pests to resistcertain pesticides, repeated applications of the molecules of FormulaOne may be desirable to control newly emerged larvae.

Systemic movement of pesticides in plants may be utilized to controlpests on one portion of the plant by applying (for example by sprayingan area) the molecules of Formula One to a different portion of theplant. For example, control of foliar-feeding insects can be achieved bydrip irrigation or furrow application, by treating the soil with forexample pre- or post-planting soil drench, or by treating the seeds of aplant before planting.

Seed treatment can be applied to all types of seeds, including thosefrom which plants genetically modified to express specialized traitswill germinate. Representative examples include those expressingproteins toxic to invertebrate pests, such as Bacillus thuringiensis orother insecticidal toxins, those expressing herbicide resistance, suchas “Roundup Ready” seed, or those with “stacked” foreign genesexpressing insecticidal toxins, herbicide resistance,nutrition-enhancement, drought resistance, or any other beneficialtraits. Furthermore, such seed treatments with the molecules of FormulaOne may further enhance the ability of a plant to better withstandstressful growing conditions. This results in a healthier, more vigorousplant, which can lead to higher yields at harvest time. Generally, about1 gram of the molecules of Formula One to about 500 grams per 100,000seeds is expected to provide good benefits, amounts from about 10 gramsto about 100 grams per 100,000 seeds is expected to provide betterbenefits, and amounts from about 25 grams to about 75 grams per 100,000seeds is expected to provide even better benefits.

It should be readily apparent that the molecules of Formula One may beused on, in, or around plants genetically modified to expressspecialized traits, such as Bacillus thuringiensis or other insecticidaltoxins, or those expressing herbicide resistance, or those with“stacked” foreign genes expressing insecticidal toxins, herbicideresistance, nutrition-enhancement, or any other beneficial traits.

The molecules of Formula One may be used for controlling endoparasitesand ectoparasites in the veterinary medicine sector or in the field ofnon-human animal keeping. The molecules of Formula One are applied, suchas by oral administration in the form of, for example, tablets,capsules, drinks, granules, by dermal application in the form of, forexample, dipping, spraying, pouring on, spotting on, and dusting, and byparenteral administration in the form of, for example, an injection.

The molecules of Formula One may also be employed advantageously inlivestock keeping, for example, cattle, sheep, pigs, chickens, andgeese. They may also be employed advantageously in pets such as, horses,dogs, and cats. Particular pests to control would be fleas and ticksthat are bothersome to such animals. Suitable formulations areadministered orally to the animals with the drinking water or feed. Thedosages and formulations that are suitable depend on the species.

The molecules of Formula One may also be used for controlling parasiticworms, especially of the intestine, in the animals listed above.

The molecules of Formula One may also be employed in therapeutic methodsfor human health care. Such methods include, but are limited to, oraladministration in the form of, for example, tablets, capsules, drinks,granules, and by dermal application.

Pests around the world have been migrating to new environments (for suchpest) and thereafter becoming a new invasive species in such newenvironment. The molecules of Formula One may also be used on such newinvasive species to control them in such new environment.

The molecules of Formula One may also be used in an area where plants,such as crops, are growing (e.g. pre-planting, planting, pre-harvesting)and where there are low levels (even no actual presence) of pests thatcan commercially damage such plants. The use of such molecules in sucharea is to benefit the plants being grown in the area. Such benefits,may include, but are not limited to, improving the health of a plant,improving the yield of a plant (e.g. increased biomass and/or increasedcontent of valuable ingredients), improving the vigor of a plant (e.g.improved plant growth and/or greener leaves), improving the quality of aplant (e.g. improved content or composition of certain ingredients), andimproving the tolerance to abiotic and/or biotic stress of the plant.

Before a pesticide can be used or sold commercially, such pesticideundergoes lengthy evaluation processes by various governmentalauthorities (local, regional, state, national, and international).Voluminous data requirements are specified by regulatory authorities andmust be addressed through data generation and submission by the productregistrant or by a third party on the product registrant's behalf, oftenusing a computer with a connection to the World Wide Web. Thesegovernmental authorities then review such data and if a determination ofsafety is concluded, provide the potential user or seller with productregistration approval. Thereafter, in that locality where the productregistration is granted and supported, such user or seller may use orsell such pesticide.

A molecule according to Formula One can be tested to determine itsefficacy against pests. Furthermore, mode of action studies can beconducted to determine if said molecule has a different mode of actionthan other pesticides. Thereafter, such acquired data can bedisseminated, such as by the internet, to third parties.

The headings in this document are for convenience only and must not beused to interpret any portion hereof.

Table Section

BAW & CEW & CL Rating Table % Control (or Mortality) Rating 50-100 AMore than 0-Less than 50 B Not Tested C No activity noticed in thisbioassay D

GPA Rating Table % Control (or Mortality) Rating 80-100 A More than0-Less than 80 B Not Tested C No activity noticed in this bioassay D

TABLE 1 Structures for Compounds Compound Number Structure AI34

AI36

AI37

AI38

AI39

AI40

AI41

AI44

AI45

AC1

AC2

AC3

AC4

AC5

AC6

AC7

AC8

AC9

AC10

AC11

AC12

AC13

AC14

AC15

AC16

AC17

AC18

AC19

AC20

AC21

AC22

AC23

AC24

AC25

AC26

AC27

AC28

AC29

AC30

AC31

AC32

AC33

AC34

AC35

AC36

AC37

AC38

AC39

AC40

AC41

AC42

AC43

AC44

AC45

AC46

AC47

AC48

AC49

AC50

AC51

AC52

AC53

AC54

AC57

AC58

AC59

AC60

AC61

AC62

AC63

AC64

AC65

AC66

AC67

AC68

AC69

AC70

AC71

AC72

AC75

AC76

AC77

AC78

AC79

AC80

AC81

AC82

AC83

AC84

AC85

AC86

AC87

AC89

AC90

AC91

AC92

AC93

AC94

AC95

AC96

AC97

AC98

AC99

AC100

AC101

AC102

AC103

AC104

AC105

AC106

AC107

AC108

AC109

AC110

AC111

AC112

AC113

AC114

AC115

AC116

AC117

AC118

BC1

BC2

BC3

BC4

BC5

BC6

BC7

BC8

BC9

BC10

BC11

BC12

BC13

BC14

CI4

CI5

CI8

CI9

CI34

CI35

CI36

CI37

CI38

CI39

CI40

CI41

CI49

CI50

CI51

CI52

CI53

CI54

CI55

CI56

CI57

CC1

CC2

CC3

CC4

CC5

CC6

CC7

CC8

CC9

CC10

CC11

CC12

CC13

CC14

CC15

CC16

CC17

CC18

CC19

CC20

CC21

CC22

CC23

CC24

CC25

CC26

CC27

CC28

CC29

CC30

CC31

CC32

CC33

CC34

CC35

CC36

CC37

CC38

CC39

CC40

CC41

CC42

CC43

CC44

CC45

CC46

CC47

CC48

CC49

CC50

CC51

CC52

CC53

CC54

DC1

DC2

DC3

DC4

DC5

DC6

DC7

DC8

DC9

DC10

DC11

DC12

DC13

DC14

DC15

DC16

DC17

DC18

DC19

DC20

DC21

DC22

DC23

DC24

DC25

DC26

DC27

DC28

DC29

DC30

DC31

DC32

DC33

DC34

DC35

DC36

DC37

DC38

DC39

DC40

DC41

DC42

DC43

DC44

DC45

DC46

DC47

DC48

DC49

DC50

DC51

DC52

DC53

DC54

DC55

DC56

DC57

DC58

DC59

DC60

DC61

DC62

DC63

DC64

DC65

DC66

DC67

DC68

DC69

DC70

TABLE 1A Structures for F Compounds Prepared according Compound toNumber Structure Appearance Example: F1

Light brown foam 128 F7

Glassy oil 128

TABLE 1B Structures for FA Compounds Prepared according Compound toNumber Structure Appearance Example: FA1

Brown gum 129 FA2

Pale rown solid 129 FA3

Brown gum 129 FA4

Brown gum 129 FA5

Pale yellow solid 129 FA6

Pale yellow gum 129 FA7

Pale yellow gum 129 FA8

Brown solid 129 FA9

Brown solid 129 FA10

Yellow- green viscous oil 135

TABLE 2 Analytical Data for Compounds in Table 1. Compound mp Number (°C.) ESIMS ¹H NMR (δ)^(a) IR (cm⁻¹) AC1 156-161 386.09 ([M − H]⁻) 7.83(m, 2H), 7.68-7.63 (m, 5H), 6.93 (dd, J = 15.6, 8.0 Hz, 1H), 6.81 (d J =15.6 Hz, 1H,), 4.15 (m, 1H), 2.80 (s, 3H) AC2 110-112 374 ([M + H]⁺)7.80 (d, J = 8.4 Hz, 2H), 7.48 (d, J = 8.0 Hz, 2H), 7.38 (m, 1H), 7.30(s, 2H), 6.65 (d, J = 16.0 Hz, 1H), 6.46 (dd, J = 16.0, 8.0 Hz, 1H),4.15 (m, 1H) AC3 162-166 402.24 ([M + H]⁺) 7.42 (m, 4H), 7.37 (t, J =1.8 Hz, 1H), 7.28 (s, 2H), 6.63 (d, J = 16.0 Hz, 1H), 6.41 (dd, J =16.0, 8.4 Hz, 1H), 4.15 (m, 1H), 3.20 (s, 3H), 3.00 (s, 3H) AC4 122-126454 ([M − H]⁻) 7.79 (d, J = 1.2 Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H), 7.38(t, J = 1.8 Hz, 1H), 7.30 (s, 2H), 6.64 (d, J = 15.6 Hz, 1H), 6.40 (dd,J = 15.6, 8.0 Hz, 1H), 6.30 (m, 1H), 4.15 (m, 3H) AC5 444.12 ([M + H]⁺)7.67 (s, 3H), 7.64 (d, J = 8.0 Hz, 2H), 7.42 (d, J = 8.0 Hz, 2H), 6.91(dd, J = 15.6, 8.0 Hz, 1H), 6.80 (d, J = 15.6 Hz, 1H), 4.80 (m, 1H),3.60 (br s, 8H) AC6 468.40 ([M − H]⁻) 7.40 (m, 2H), 7.26 (m, 1657, 1113,3H), 6.56 (d, J = 16.0 Hz, 804 1H), 6.48 (dd, J = 16.0, 8.0 Hz, 1H),5.82 (br s, 1H), 4.08 (m, 3H), 2.52 (s, 3H) AC7 511.02 ([M − H]⁻) 8.39(s, 1H), 7.74 (m, 3276, 1645, 1H), 7.39 (m, 3H), 1111, 801 7.24 (m, 4H),6.58 (d, J = 16.0 Hz, 1H), 6.38 (dd, J = 16.0, 8.0 Hz, 1H), 6.16 (br s,1H), 4.63 (m, 2H), 4.12 (m, 1H), 2.41 (s, 3H) AC8 454.11 ([M − H]⁻) 7.39(s, 1H), 7.22 (m, 1748, 1112, 2H), 7.19 (m, 3H), 801 6.53 (d, J = 16.0Hz, 1H), 6.39-6.34 (dd, J = 16.0, 8.0 Hz, 1H), 4.22 (m, 1H), 3.95 (t, J= 7.0 Hz, 2H), 2.62 (t, J = 8.0 Hz, 2H), 2.30 (s, 3H), 2.18 (m, 2H) AC9494.02 ([M − H]⁻) 7.45 (t, J = 7.6 Hz, 1H), 3276, 1645, 7.36 (m, 2H),7.21 (m, 1112, 801 3H), 7.15 (m, 4H), 6.56 (d, J = 16.0 Hz, 1H), 6.38(dd, J = 16.0, 8.4 Hz, 1H), 6.08 (br s, 1H), 4.68 (d, J = 5.6 Hz, 2H),4.11 (m, 1H), 2.44 (s, 3H) A10 140-143 458.00 ([M − H]⁻) 7.38 (t, J =1.6 Hz, 1H), 7.34 (d, J = 7.6 Hz, 1H), 7.27 (m, 2H), 7.24 (m, 2H), 6.57(d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 6.16 (m 1H), 5.44(m, 1H), 4.12 (m, 1H), 3.51 (m, 2H), 3.40 (m, 2H), 2.44 (s, 3H) AC11476.17 ([M − H]⁻) 7.39-7.29 (m, 9H), 3287, 1644, 7.24 (m, 2H), 6.56 (d,J = 16.0 Hz, 1112, 801 1H), 6.38 (dd, J = 16.0, 8.0 Hz, 1H), 5.99 (br s,1H), 4.63 (d, J = 6.0 Hz, 1H), 4.11 (m, 1H), 2.47 (s, 3H) AC12 479.30([M + H]⁺) 8.63 (d, J = 4.4 Hz, 1H), 3293, 1653, 7.71 (m, 1H), 7.47 (d,J = 8.4 Hz, 1112, 800 1H), 7.37 (m, 2H), 7.32 (m, 2H), 7.23 (m, 2H),7.13 (m, 1H), 6.58 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz,1H), 4.75 (d, J = 4.8 Hz, 2H), 4.12 (m, 1H), 2.49 (s, 3H) AC13 75-78490.04 ([M − H]⁻) 7.38 (m, 2H), 7.27 (m, 3H), 7.23 (br s, 1H), 6.58 (d,J = 16.0 Hz, 1H), 6.45 (m 1H), 6.42 (dd, J = 16.0, 8.4 Hz, 1H), 4.91 (m1H), 4.64 (m, 2H), 4.14 (m, 1H), 4.04 (m, 2H), 2.46 (s, 3H) AC14 480.99([M + 2H]⁺) 8.63 (s, 2H), 7.76 (d, J = 8.0 Hz, 3293, 1645, 1H), 7.36 (m,1113, 800 3H), 7.22 (m, 1H), 7.13 (m, 2H), 6.57 (d, J = 16.0 Hz, 1H),6.39 (dd, J = 16.0, 8.0 Hz, 1H), 6.13 (br s, 1H), 4.66 (d, J = 5.6 Hz,2H), 4.11 (m, 1H), 2.46 (s, 3H) AC15 59-61 516.86 ([M − H]⁻) 7.45 (s,1H), 7.37 (m, 3246, 1635, 1H), 7.34 (m, 1H), 1112, 801 7.26 (m, 3H),7.22 (m, 1H), 6.57 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz,1H), 6.18 (m, 1H), 4.71 (d, J = 6.4 Hz, 2H), 4.11 (m, 1H), 2.46 (s, 3H)AC16 506.93 ([M + H]⁺) 8.47 (m, 1H), 8.19 (s, 1657, 1113, 1H), 7.76 (m,1H), 801 7.47 (m, 2H), 7.37 (m, 1H), 7.28 (m, 2H), 7.24 (m, 1H), 7.21(m, 1H), 6.59 (d, J = 16.0 Hz, 1H), 6.39 (dd, J = 16.0, 8.4 Hz, 1H),4.12 (m, 1H), 2.48 (s, 3H), 1.88 (s, 6H) AC17 70-73 494.98 ([M − H]⁻)7.49 (m, 2H), 7.38 (m, 1H), 7.29 (m, 4H), 7.08 (m, 3H), 6.91 (m, 1H),6.61 (d, J = 16.0 Hz, 1H), 6.48 (m, 1H), 6.43 (dd, J = 16.0, 8.0 Hz,1H), 4.13 (m, 1H), 2.49 (s, 3H) AC18 155-158 480.44 ([M + H]⁺) 8.73 (d,J = 4.8 Hz, 2H), 7.53 (d, J = 8.4 Hz, 1H), 7.37 (m, 1H), 7.27 (m, 4H),7.23 (m, 1H), 7.11 (m, 1H), 6.60 (d, J = 16.0 Hz, 1H), 6.41 (dd, J =16.0, 8.0 Hz, 1H), 4.90 (d, J = 4.8 Hz, 2H), 4.13 (m, 1H), 2.52 (s, 3H)AC19 55-57 471.66 ([M + H]⁺) 7.37 (m, 1H), 7.33 (d, J = 7.6 Hz, 1H),7.27 (m, 2H), 7.22 (m, 2H), 6.57 (d, J = 16.0 Hz, 1H), 6.39 (dd, J =16.0, 8.0 Hz, 1H), 6.10 (brs, 1H), 4.13 (m, 2H), 3.94 (m, 1H), 3.79 (m,2H), 3.35 (m, 1H), 2.45 (s, 3H), 2.14 (m, 1H), 1.71 (m, 2H), 1.65 (m,1H). AC20 467.68 ([M + H]⁺) 7.37 (m, 2H), 7.27 (m, 3437, 1664, 2H), 7.23(m, 2H), 1265, 1114, 6.57 (d, J = 16.0 Hz, 1H), 746 6.38 (m, 3H), 6.01(m, 1H), 4.63 (d, J = 5.6 Hz, 2H), 4.13 (m, 1H), 2.45 (s, 3H) AC21 61-64528.78 ([M + H]⁺) 8.44 (s, 1H), 8.18 (s, 1H), 7.83 (br s, 1H), 7.38 (m,2H), 7.27 (m, 2H), 7.25 (m, 2H), 7.21 (m, 1H), 6.57 (d, J = 16.0 Hz,1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 5.01 (s, 2H), 4.11 (m, 1H), 2.43(s, 3H) AC22 545.08 ([M − H]⁻) 8.39 (s, 1H), 7.73 (m, 3270, 1642, 1H),7.40 (s, 1H), 1111, 809 7.35 (m, 2H), 7.22 (m, 3H), 6.57 (d, J = 16.0Hz, 1H), 6.38 (dd, J = 16.0, 7.6 Hz, 1H), 6.14 (br s, 1H), 4.62 (d, J =6.0 Hz, 2H), 4.13 (m, 1H), 2.45 (s, 3H) AC23 492.35 ([M − H]⁻) 7.42 (s,2H), 7.36 (m, 3273, 1641, 1H), 7.24 (m, 2H), 1250, 1113, 6.59 (d, J =16.0 Hz, 1H), 807 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 6.20 (br s, 1H), 5.46(m, 1H), 4.15 (m, 1H), 3.52 (m, 2H), 3.41 (m, 2H), 2.45 (s, 3H) AC24129-132 526.98 ([M + H]⁺) 7.40 (m, 2H), 7.27 (m, 3298, 1664, 2H), 7.25(m, 2H), 1113, 803 6.92 (br s, 2H), 6.60 (m, 1H), 6.48 (dd, J = 16.0,8.0 Hz, 1H), 4.19 (d, J = 5.2, 2H), 4.08 (m, 1H), 3.99 (m, 2H), 2.46 (s,3H) AC25 542.24 ([M − H]⁻) 7.41 (m, 3H), 7.27 (m, 3257, 1652, 2H), 6.58(d, J = 15.6 Hz, 1316, 1109, 1H), 6.42 (m, 2H), 807 4.92 (m, 1H), 4.65(m, 2H), 4.14 (m, 1H), 4.09 (m, 2H), 2.46 (s, 3H) AC26 550.69 ([M − H]⁻)7.45 (s, 1H), 7.40 (s, 3255, 1638, 2H), 7.34 (d, J = 8.0 Hz, 1113, 8091H), 7.22 (m, 2H), 6.54 (d, J = 16.0 Hz, 1H), 6.38 (dd, J = 16.0, 8.0Hz, 1H), 4.71 (d, J = 6.0 Hz, 2H), 4.11 (m, 1H), 2.46 (s, 3H) AC27541.00 ([M − H]⁻) 8.46 (d, J = 4.0 Hz, 1H), 1653, 1113, 8.20 (s, 1H),7.76 (m, 809 1H), 7.47 (m, 2H), 7.41 (s, 2H), 7.23 (m, 2H), 7.21 (m,1H), 6.59 (d, J = 16.0 Hz, 1H), 6.37 (dd, J = 16.0, 8.4 Hz, 1H), 4.11(m, 1H), 2.48 (s, 3H), 1.88 (s, 6H) AC28 65-67 564.84 ([M − H]⁻) 8.40(s, 1H), 7.74 (m, 3267, 1650, 2H), 7.42 (m, 3H), 1112, 809 7.36 (m, 2H),6.72 (br s, 1H), 6.52 (d, J = 16.0 Hz, 1H), 6.43 (dd, J = 16.0, 8.0 Hz,1H), 4.66 (d, J = 6.4 Hz, 2H), 4.12 (m, 1H) AC29 75-78 511.78 ([M − H]⁻)7.71 (d, J = 8.4 Hz, 1H), 7.42 (m, 3H), 7.35 (m, 1H), 6.75 (br s, 1H),6.56 (d, J = 16.0 Hz, 1H), 6.43 (dd, J = 16.0, 8.0 Hz, 1H), 5.49 (m,1H), 4.14 (m, 1H), 3.50 (m, 4H) AC30 110-113 543.72 ([M − H]⁻) 7.42 (d,J = 8.4 Hz, 1H), 7.44 (s, 1H), 7.40 (s, 1H), 7.38 (m, 1H), 7.06 (br s,1H), 6.58 (d, J = 15.6 Hz, 1H), 6.45 (dd, J = 15.6, 8.0 Hz, 1H), 4.93(m, 1H), 4.65 (m, 2H), 4.13 (m, 3H) AC31 68-70 610.73 ([M + H]⁺) 8.42(s, 1H), 7.76 (m, 1H), 7.61 (m, 2H), 7.39 (m, 4H), 6.54-6.39 (m, 3H),4.66 (d, J = 6.0 Hz, 2H), 4.12 (m, 1H) AC32 78-80 555.89 ([M − H]⁻) 7.61(m, 2H), 7.40 (m, 3H), 6.54 (m, 2H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H),5.46 (m, 1H), 4.14 (m, 1H), 3.50 (m, 4H) AC33 182-184 587.68 ([M − H]⁻)7.62 (s, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.40 (m, 3H), 6.84 (br s, 1H),6.55 (d, J = 15.6 Hz, 1H), 6.45 (dd, J = 15.6, 7.6 Hz, 1H), 4.93 (m 1H),4.65 (m, 2H), 4.13 (m, 4H) AC34 151-153 545.83 ([M − H]⁻) 7.67 (s, 1H),7.61 (d, J = 6.0 Hz, 1H), 7.53 (m, 1H), 7.41 (s, 2H), 6.64 (d, J = 16.0Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 6.18 (br s, 1H), 5.44 (m, 1H),4.14 (m, 1H), 3.50 (m, 2H), 3.40 (m, 2H) AC35 100-102 577.71 ([M − H]⁻)7.70 (s, 1H), 7.63 (m, 3257, 1655, 1H), 7.53 (d, J = 7.6 Hz, 1113, 8081H), 7.41 (s, 2H), 6.53 (d, J = 16.0 Hz, 1H), 6.49 (m, 2H), 4.93 (m,1H), 4.64 (m, 2H), 4.13 (m, 1H), 4.03 (m, 2H) AC36 81-83 600.83 ([M +H]⁺) 8.40 (s, 1H), 7.73 (m, 2H), 7.61 (d, J = 8.4 Hz, 1H), 7.52 (d, J =8.0 Hz, 1H), 7.40 (s, 2H), 7.35 (d, J = 8.0 Hz, 1H), 6.63 (d, J = 16.0Hz, 1H), 6.46 (dd, J = 16.0, 7.6 Hz, 1H), 6.14 (m, 1H), 4.63 (d, J = 6.0Hz, 2H), 4.14 (m, 1H) AC37 512.68 ([M + H]⁺) 8.39 (s, 1H), 7.73 (m,3268, 1644, 1H), 7.48 (m, 2H), 1109, 820 7.34 (d, J = 7.6 Hz, 1H), 7.24(m, 3H), 6.55 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0, 7.6 Hz, 1H),6.12 (m, 1H), 4.62 (d, J = 6.0 Hz, 2H), 4.13 (m, 1H), 2.45 (s, 3H) AC3879-80 528.85 ([M − H]⁻) 8.46 (m, 1H), 7.73 (m, 1H), 7.35 (m, 4H), 7.22(m, 2H), 6.56 (d, J = 16.0 Hz, 1H), 6.38 (dd, J = 16.0, 8.0 Hz, 1H),4.62 (d, J = 6.0 Hz, 2H), 4.10 (m, 1H), 2.45 (s, 3H) AC39 141-144 477.83([M − H]⁻) 9.19 (s, 1H), 8.79 (s, 2H), 7.37 (m, 2H), 7.23 (m, 2H), 7.21(m, 1H), 6.57 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 7.6 Hz 1H), 6.21(m, 1H), 4.65 (s, 2H), 4.11 (m, 1H), 2.46 (s, 3H) AC40 69-72 484.67([M + H]⁺) 8.33 (t, J = 5.6 Hz, 1H), 8.61 (m, 1H), 7.68 (m, 3H), 7.48(m, 2H), 6.86 (dd, J = 15.6, 8.2 Hz 1H), 6.74 (d, J = 15.6 Hz, 1H), 4.44(m, 1H), 3.76 (d, J = 6.0 Hz, 2H), 2.54 (m, 1H), 2.67 (s, 3H), 0.59 (m,2H), 0.54 (m, 2H) AC41 196-199 515.00 ([M − H]⁻) 8.66 (d, J = 7.6 Hz,1H), 8.39 (t, J = 5.6 Hz, 1H), 7.65 (s, 3H), 7.45 (m, 3H), 6.86 (dd, J =15.6, 8.8 Hz, 1H), 6.74 (d, J = 15.6 Hz, 1H), 5.01 (m, 1H), 4.99 (m,1H), 3.78 (d, J = 6.0 Hz, 2H), 3.40 (m, 2H), 3.22 (m, 2H), 2.37 (m, 3H)AC42 79-82 534.72 ([M + H]⁺) 7.99 (d, J = 8.0 Hz, 1H), 7.89 (d, J = 8.0Hz, 1H), 7.51 (m, 2H), 7.44 (m, 2H), 7.27 (m, 4H), 6.71 (t, J = 5.2 Hz,1H), 6.59 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0, 8.0 Hz, 1H), 5.05(d, J = 1.6 Hz, 2H), 4.12 (m, 1H), 2.52 (m, 3H) AC43 481.75 ([M + H]⁺)8.69 (s, 1H), 8.52 (s, 1663, 2H), 7.45 (d, J = 7.6 Hz, 1608, 1168, 1H),7.37 (d, J = 2.0 Hz, 1114, 801 1H), 7.26 (m, 2H), 7.21 (m, 1H), 6.83 (s,1H), 6.58 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.4 Hz, 1H), 4.81(d, J = 5.6 Hz, 2H), 4.12 (t, J = 8.4 Hz 1H), 2.45 (s, 3H) AC44 528.01([M + H]⁺) 8.44 (d, J = 2.4 Hz, 1H), 1640, 1166, 7.69 (d, J = 2.4 Hz,1112, 800 1H), 7.37 (m, 1H), 7.33 (s, 1H), 7.31 (s, 1H), 7.26 (m, 1H),7.24 (m, 3H), 6.57 (d, J = 16.0 Hz, 1H), 6.39 (dd, J = 16.0, 8.0 Hz,1H), 5.96 (d, J = 7.2 Hz, 1H), 5.32 (t, J = 7.2 Hz, 1H), 4.11 (t, J =8.4 Hz, 1H), 2.41 (s, 3H), 1.61 (d, J = 7.2 Hz, 3H) AC45 512.88 ([M +H]⁺) 7.66 (s, 1H), 7.37 (d, J = 6.8 Hz, 1657, 1167, 2H), 7.26 (m, 1106,800 3H), 7.18 (m, 1H), 7.11 (m, 2H), 6.99 (m, 1H), 6.57 (d, J = 15.6 Hz,1H), 6.39 (dd, J = 15.6, 8.0 Hz, 1H), 4.11 (t, J = 8.4 Hz, 1H), 3.36 (s,3H), 2.43 (s, 3H) AC46 61-64 575.93 ([M + H]⁺) 8.42 (d, J = 2.0 Hz, 1H),7.76 (d, J = 2.4 Hz, 1H), 7.61 (m, 2H), 7.39 (m, 3H), 7.26 (s, 2H), 6.54(d, J = 16.0 Hz, 1H), 6.42 (dd, J = 16.0, 7.6 Hz, 1H), 4.65 (d, J = 6.0Hz, 2H), 4.14 (m, 1H) AC47 525.89 ([M − H]⁻) 10.02 (s, 1H), 9.87 (s,3280, 1640 1H), 8.47 (t, J = 6.0 Hz, 1H), 7.66 (s, 3H), 7.44 (s, 1H),7.40 (d, J = 3.6 Hz, 2H), 6.86 (dd, J = 15.6, 9.2 Hz, 1H), 6.74 (d, J =15.6 Hz, 1H), 4.82 (t, J = 9.6 Hz, 2H), 3.88 (d, J = 6.0 Hz, 2H), 2.36(s, 3H), 1.63 (m, 1H), 0.76 (m, 4H) AC48 509.96 ([M − H]⁻) 7.37 (m, 7H),7.34 (m, 3275, 1642 3H),, 6.57 (d, J = 16.0 Hz, 1H), 6.39 (dd, J = 16.0,8.0 Hz, 1H), 6.01 (m, 1H), 4.60 (d, J = 6.0 Hz, 2H), 4.13 (m, 1H), 2.46(s, 3H) AC49 518.85 ([M + H]⁺) 8.39 (d, J = 2.0 Hz, 1H), 1658, 1112,8.11 (m, 1H), 7.71 (d, J = 2.4 Hz, 1025, 2219 1H), 7.41 (m, 3H), 7.17(m, 3H), 6.59 (d, J = 16.0 Hz, 1H), 6.47 (dd, J = 16.0, 8.0 Hz, 1H),4.66 (d, J = 5.6 Hz, 2H), 4.14 (m, 1H) AC50 481.88 ([M + H]⁺) 8.72 (m,1H), 7.67 (s, 1654, 1112, 3H), 7.46 (s, 1H), 800, 3069 7.40 (m, 2H),7.08 (s, 1H), 6.82 (m, 2H), 6.55 (d, J = 7.6 Hz, 1H), 4.82 (m, 1H), 4.48(s, 2H), 3.65 (s, 3H), 2.38 (s, 3H) AC51 540.83 ([M + H]⁺) 7.45 (d, J =7.6 Hz, 1H), 1652, 1571, 7.38 (m, 1H), 7.27 (m, 802, 1114, 2H), 7.22 (m,2H), 2926 6.85 (m, 1H), 6.58 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0,8.0 Hz, 1H), 4.33 (m, 2H), 4.14 (m, 3H), 3.18 (s, 3H), 2.48 (s, 3H) AC52488.29 ([M − H]⁻) 7.33 (m, 2H), 7.25 (m, 1635, 11134, 3H), 6.56 (d, J =15.6 Hz, 813, 2927 1H), 6.37 (dd, J = 15.6, 8.0 Hz, 1H), 5.61 (d, J =8.0 Hz, 1H), 4.21 (m, 1H), 4.01 (m, 1H), 4.08 (m, 2H), 3.56 (t, J = 10.0Hz, 2H), 2.48 (m, 2H), 2.08 (m, 2H), 1.5 (m, 3H) AC53 532.92 ([M + H]⁺)8.49 (d, J = 2.0 Hz, 1H), 1651, 3027, 7.69 (d, J = 2.4 Hz, 1H), 815,1113 7.43 (d, J = 8.0 Hz, 1H), 7.34 (m, 3H), 7.26 (m, 2H), 6.95 (m, 1H),6.58 (d, J = 16.0 Hz, 1H), 6.38 (dd, J = 16.0, 8.0 Hz, 1H), 4.72 (d, J =5.2 Hz, 2H), 4.09 (m, 1H), 2.47 (s, 3H) AC54 529.06 ([M − H]⁻) 8.37 (d,J = 5.2 Hz, 1H), 1654, 3434, 7.41 (d, J = 8.0 Hz, 1H), 814, 1112 7.36(m, 3H), 7.31 (m, 1H), 7.26 (m, 2H), 6.58 (d, J = 16.0 Hz, 1H), 6.40(dd, J = 16.0, 7.6 Hz, 1H), 5.20 (t, J = 5.6 Hz, 1H), 4.63 (d, J = 6.0Hz, 2H), 4.13 (m, 1H), 2.18 (s, 3H) AC57 464.96 ([M + H]⁺) 8.69 (t, J =6.0 Hz, 1H), 3417, 1658, 8.58 (t, J = 6.0 Hz, 1H), 1165, 817 7.92 (s,1H), 7.87 (d, J = 6.4 Hz, 2H), 7.62 (d, J = 8.4 Hz, 1H), 7.45 (d, J =8.4 Hz, 1H), 7.0 (m, 1H), 6.76 (d, J = 15.6 Hz, 1H), 6.76 (dd, J = 15.6,8.0 Hz, 1H), 4.01 (m, J = 8.0 Hz, 1H), 3.71 (m, 2H), 3.49 (m, 2H) AC58124.4-126.9 599.76 ([M + H]⁺) 7.62 (m, 2H), 7.40 (s, 2H), 7.37 (d, J =1.6 Hz, 1H), 6.61 (t, J = 4.8 Hz, 1H), 6.55 (d, J = 16.0 Hz, 1H), 6.41(dd, J = 16.0, 7.6 Hz, 1H), 4.16 (d, J = 6.0 Hz, 2H), 4.01 (m, 1H), 1.56(s, 9H) AC59 80-83 497.40 ([M − H]⁻) 8.42 (d, J = 2.1 Hz, 1H), 8.29 (d,J = 7.5 Hz, 1H), 7.51 (m, 2H), 7.39 (m, 1H), 7.36 (m, 4H), 7.28 (m, 1H),6.61 (d, J = 15.9 Hz, 1H), 6.45 (dd, J = 15.9, 7.8 Hz 1H), 4.14 (t, J =8.4 Hz, 1H), 2.51 (s, 3H) AC60 515.09 ([M + H]⁻) 8.52 (s, 1H), 8.39 (d,J = 1.8 Hz, 1668, 1589, 2H), 7.70 (d, J = 2.1 Hz, 1167, 1113, 1H), 7.62(s, 802 1H), 7.43 (s, 1H), 7.35 (m, 3H), 6.62 (d, J = 16.2 Hz, 1H), 6.52(dd, J = 16.2, 7.5 Hz, 1H), 4.62 (d, J = 6.3 Hz, 2H), 4.19 (m, 1H), 2.76(s, 3H) AC61 461.90 ([M − H]⁻) 8.07 (t, J = 8.0 Hz, 1H), 1658, 1114,7.39 (t, J = 2.0 Hz, 1H), 801 7.28 (d, J = 1.2 Hz, 3H), 7.17 (d, J = 1.6Hz, 1H), 7.11 (m, 1H), 6.59 (d, J = 15.6 Hz, 1H), 6.47 (dd, J = 15.6,7.6 Hz, 1H), 5.49 (m, 1H), 4.14 (t, J = 8.4 Hz, 1H), 3.48 (m, 4H) AC62105-108 528.88 ([M − H]⁻) 8.62 (t, J = 6.4 Hz, 1H), 8.46 (m, 1H), 7.73(m, 5H), 7.48 (d, J = 7.6 Hz, 1H), 7.03 (dd, J = 15.6, 9.2 Hz, 1H), 6.81(d, J = 15.6 Hz, 1H), 4.86 (m, 1H), 3.97 (m, 4H) AC63 77-80 594.67 ([M +H]⁺) 8.43 (s, 1H), 7.76 (d, J = 2.4 Hz, 3257, 1653 1H), 7.60 (m, 2H),7.38 (d, J = 7.6 Hz, 1H), 7.33 (d, J = 6.4 Hz, 3H), 6.54 (d, J = 16.0Hz, 1H), 6.46 (m, 1H), 6.41 (dd, J = 16.0 8.0 Hz, 1H), 4.65 (d, J = 6.0Hz, 2H), 4.15 (m, 1H) AC64 83-85 580.72 ([M − H]⁻) 7.72 (d, J = 8.0 Hz,1H), 7.44 (s, 1H), 7.40 (s, 2H), 7.36 (d, J = 6.8 Hz, 1H), 7.05 (t, J =5.2 Hz, 1H), 6.70 (t, J = 5.2 Hz, 1H), 6.57 (d, J = 15.6 Hz, 1H), 6.44(dd, J = 15.6, 8.0 Hz, 1H), 4.23 (d, J = 5.6 Hz, 2H), 4.15 (m, 1H), 4.01(m, 2H) AC65 534.72 ([M − H]⁻) 8.39 (d, J = 2.0 Hz, 1658, 1113, 1H),8.12 (t, J = 8.4 Hz, 817, 2925 1H), 7.71 (d, J = 2.4 Hz, 1H), 7.34 (m,3H), 7.26 (m, 1H), 7.11 (m, 2H), 6.59 (d, J = 16.0 Hz, 1H), 6.46 (dd, J= 16.0, 8.0 Hz, 1H), 4.66 (d, J = 5.2 Hz, 2H), 4.13 (m, 1H) AC66 73-75624.61 ([M − H]⁻) 7.88 (s, 1H), 7.63 (d, J = 1.6 Hz, 1H), 7.57 (d, J =8.0 Hz, 1H), 7.40 (m, 2H), 6.80 (t, J = 5.6 Hz, 1H), 6.70 (t, J = 5.6Hz, 1H), 6.56 (d, J = 16.0 Hz, 1H), 6.44 (dd, J = 16.0, 8.0 Hz, 1H),4.22 (m, 2H), 4.12 (m, 1H), 4.01 (m, 2H) AC67 479.82 ([M − H]⁻) 8.07 (t,J = 8.0 Hz, 1H), 3272, 1644 7.34 (d, J = 6.0 Hz, 2H), 7.28 (s, 1H), 7.17(s, 2H), 6.59 (d, J = 15.6 Hz, 1H), 6.46 (dd, J = 15.6, 8.0 Hz, 1H),5.49 (m, 1H),, 4.12 (m, 1H), 3.49 (m, 4H). AC68 90-93 546.80 ([M − H]⁻)8.6 (t, J = 6.4 Hz, 1H), 3315, 1684 8.45 (m, 1H), 7.86 (d, J = 6.4 Hz,2H), 7.75 (t, J = 8.0 Hz, 1H), 7.63 (d, J = 12.0 Hz, 1H), 7.48 (d, J =8.0 Hz, 1H), 7.03 (dd, J = 15.6, 9.6 Hz, 1H), 6.80 (d, J = 15.6 Hz, 1H),4.88 (m, 1H), 3.96 (m, 4H) AC69 542.82 ([M − H]⁻) 7.41 (d, J = 8.0 Hz,1H), 3294, 1685 7.34 (d, J = 5.6 Hz, 2H), 7.26 (m, 1H), 7.23 (m, 1H),6.81 (s, 1H), 6.57 (d, J = 15.6 Hz, 1H), 6.55 (s, 1H), 6.39 (dd, J =15.6, 8.0 Hz, 1H), 4.18 (m, 2H), 4.13 (m, 1H), 3.97 (m, 2H), 2.46 (s,3H) AC70 176-178 545.23 ([M − H]⁻) 8.38 (d, J = 2.4 Hz, 1H), 8.22 (d, J= 6.8 Hz, 2H), 7.71 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 6.0 Hz, 2H), 7.30(d, J = 7.6 Hz, 1H), 7.15 (d, J = 1.6 Hz, 1H), 6.93 (d, J = 1.2 Hz, 1H),6.60 (d, J = 15.6 Hz, 1H), 6.43 (dd, J = 15.6, 7.6 Hz, 1H), 4.66 (d, J =6.0 Hz, 2H), 4.13 (m, 1H), 3.98 (s, 3H) AC71 492.20 ([M − H]⁻) 8.24 (d,J = 7.6 Hz, 1H), 1639, 3079, 8.15 (d, J = 8.4 Hz, 1H), 858 7.35 (d, J =6.0 Hz, 2H), 7.13 (d, J = 1.2 Hz, 1H), 6.92 (s, 1H), 6.61 (d, J = 16.0Hz, 1H), 6.43 (dd, J = 16.0, 7.6 Hz, 1H), 5.48 (m, 1H), 4.13 (m, 1H),4.03 (s, 3H), 3.48 (m, 4H) AC72 543.05 ([M − H]⁻) 8.42 (d, J = 2.4 Hz,1H), 1642, 3246, 7.75 (d, J = 2.4 Hz, 1H), 814, 1113 7.34 (m, 4H), 7.20(m, 2H), 6.60 (d, J = 16.0 Hz, 1H), 6.36 (dd, J = 16.0, 8.0 Hz, 1H),6.12 (t, J = 5.6 Hz, 1H), 4.62 (d, J = 6.0 Hz, 2H), 4.20 (m, 1H), 2.82(m, 2H), 1.45 (t, J = 5.6 Hz, 3H) AC75 644.78 ([M + H]⁺) 8.72 (s, 1H),7.97 (d, J = 7.2 Hz, 3431, 1652, 1H), 7.70 (d, J = 8.4 Hz, 1171, 8091H), 7.61 (m, 2H), 7.40 (m, 2H), 6.55 (m, 2H), 6.42 (dd, J = 16.0, 8.0Hz, 1H), 4.76 (d, J = 6.0 Hz, 2H), 4.12 (m, 1H) AC76 531.34 ([M + H]⁺)8.87 (t, J = 6.0 Hz, 1H), 3120, 1708, 8.34 (d, J = 2.1 Hz, 1H), 11717.85 (d, J = 6.3 Hz, 3H), 7.48 (m, 4H), 6.57 (d, J = 15.6 Hz, 1H), 6.45(dd, J = 15.6, 9.0 Hz, 1H), 4.84 (m, 1H), 4.49 (d, J = 5.7 Hz, 2H), 2.82(m, 2H), 2.36 (t, J = 5.6 Hz, 3H) AC77 531.1 ([M + H]⁺) 8.87 (t, J = 6.0Hz, 1H), 3444, 1648, 8.34 (d, J = 2.1 Hz, 1H), 1114, 814 7.85 (d, J =6.3 Hz, 3H), 7.48 (m, 4H), 6.57 (d, J = 15.6 Hz, 1H), 6.45 (dd, J =15.6, 8.0 Hz, 1H), 4.84 (m, 1H), 4.49 (d, J = 5.7 Hz, 2H), 2.36 (s, 3H)AC78 561.06 ([M + H]⁺) 8.59 (t, J = 6.4 Hz, 1H), 3432, 1631, 8.47 (t, J= 5.6 Hz, 1H), 1161, 840 7.89 (s, 2H), 7.45 (m, 3H), 6.87 (m, 1H), 6.75(d, J = 15.6 Hz, 1H), 4.85 (t, J = 8.0 Hz 1H), 3.98 (m, 4H), 2.58 (s,3H) AC79 610.97 ([M + H]⁺) 8.69 (t, J = 6.0 Hz, 1H), 3303, 1658, 8.58(t, J = 6.0 Hz, 1H), 1166, 817 7.92 (s, 1H), 7.87 (d, J = 6.4 Hz, 2H),7.62 (d, J = 8.4 Hz, 1H), 7.45 (d, J = 8.4 Hz, 1H), 7.0 (m, 1H), 6.76(d, J = 15.6 Hz, 1H) 4.83 (t, J = 8.0 Hz, 1H), 3.98 (m, 4H) AC80 561.06([M + H]⁺) 7.37 (m, 3H), 7.26 (m, 3412, 1624, 1H), 7.24 (m, 1H), 1157,825 6.59 (d, J = 15.6 Hz, 1H), 6.39 (dd, J = 15.6, 8.0 Hz, 1H), 4.24 (m,4H), 3.90 (m, 1H), 2.83 (m, 2H), 1.26 (m, 3H) AC81  9-92 546.93 ([M −H]⁻) 8.73 (d, J = 5.6 Hz, 1H), 8.45 (t, J = 6.0 Hz, 1H), 7.76 (s, 3H),7.45 (m, 3H), 6.86 (dd, J = 16.0, 9.2 Hz, 1H), 4.83 (m, 1H), 4.56 (m,2H), 4.51 (m, 1H), 4.10 (m, 2H), 3.85 (d, J = 6.0 Hz, 2H), 2.50 (m, 3H)AC82 477.69 ([M + H]⁺) 7.38 (d, J = 1.8 Hz, 1646, 1353, 2H), 7.33 (s,1H), 1196, 1112, 7.27 (s, 3H), 6.58 (d, J = 16.0 Hz, 800 1H), 6.42 (d, J= 8.1 Hz, 1H), 6.36 (dd, J = 16.0, 7.8 Hz, 1H), 4.71 (m, 1H), 4.23 (m,3H), 3.26 (m, 2H), 2.45 (s, 3H) AC83 493.83 ([M − H]⁻) 8.07 (t, J = 8.4Hz, 1H), 1527, 1113, 7.39 (t, J = 1.6 Hz, 1H), 801, 1167, 7.31 (d, J =1.2 Hz, 1H), 1321 7.26 (m, 2H), 7.23 (m, 1H), 7.19 (d, J = 1.6 Hz, 1H),6.60 (d, J = 16.8 Hz, 1H), 6.49 (dd, J = 16.8, 7.6 Hz, 1H), 4.90 (m,1H), 4.64 (m, 2H), 4.14 (m, 2H), 4.10 (m, 1H) AC84 511.75 ([M − H]⁻)8.07 (t, J = 8.0 Hz, 1H), 1645, 1113, 7.34 (m, 3H), 7.19 (d, J = 13.2Hz, 804, 3030, 1H), 6.60 (d, 1245 J = 16.4 Hz, 1H), 6.48 (dd, J = 16.4,8.0 Hz, 1H), 4.88 (m, 1H), 4.62 (m, 2H), 4.12 (m, 3H) AC85 523.83 ([M −H]⁻) 8.60 (d, J = 6.8 Hz, 1H), 1652, 3039, 8.15 (d, J = 8.4 Hz, 1H),802, 1114 7.35 (d, J = 6.0 Hz, 1H), 7.15 (d, J = 7.2 Hz, 1H), 6.94 (s,1H), 6.60 (d, J = 15.6 Hz, 1H), 6.44 (dd, J = 7.6, 7.6 Hz, 1H), 4.93 (m,1H), 4.62 (m, 2H), 4.13 (m, 6H) AC86 524.36 ([M + H]⁺) 7.35 (d, J = 6.3Hz, 3H), 3333, 1651, 7.26 (m, 2H), 7.20 (m, 815 1H), 6.60 (d, J = 15.9Hz, 1H), 6.47 (dd, J = 15.9, 6.6 Hz, 1H), 4.86 (m, 1H), 4.65 (m, 2H),4.13 (m, 3H), 2.84 (q, 2.8 Hz, 2H), 1.26 (m, 3H) AC87 495.82 ([M − H]⁻)8.07 (t, J = 8.0 Hz, 1H), 1623, 1114, 7.52 (m, 3H), 7.19 (d, J = 13.2Hz, 816 1H), 6.59 (d, J = 16.4 Hz, 1H), 6.47 (dd, J = 16.4, 8.0 Hz, 1H),4.69 (m, 1H), 4.23 (m, 3H), 3.29 (m, 2H) AC89 509.89 ([M + H]⁺) 7.43 (m,2H), 7.27 (m, 1666, 1166, 2H), 7.23 (m, 2H), 1112, 800 6.58 (d, J = 16.0Hz, 1H), 6.41 (dd, J = 16.0, 7.6 Hz, 1H), 4.79 (d, J = 5.6 Hz, 2H), 4.14(m, 1H), 2.48 (s, 3H), 2.18 (m, 1H), 1.16 (m, 4H) AC90 656.9 ([M − H]⁻)8.34 (m, 1H), 8.27 (m, 1H), 7.60 (d, J = 1.6 Hz, 1H), 7.49 (d, J = 8.0Hz, 2H), 7.40 (s, 2H), 7.36 (dd, J = 8.2, 1.7 Hz, 1H), 6.53 (d, J = 16.0Hz, 1H), 6.38 (dd, J = 15.9, 7.9 Hz, 1H), 4.89 (d, J = 8.4 Hz, 2H), 4.48(d, J = 9.0 Hz, 2H), 4.11 (m, 1H) AC91 640.9 ([M − H]⁻) 8.18 (t, J = 5.0Hz, 1H), 7.58 (d, J = 1.6 Hz, 1H), 7.47 (d, J = 8.0 Hz, 1H), 7.40 (s,2H), 7.34 (dd, J = 8.1, 1.6 Hz, 1H), 6.52 (m, 2H), 6.37 (dd, J = 15.9,7.9 Hz, 1H), 4.54 (d, J = 4.9 Hz, 2H), 4.12 (m, 1H), 3.99 (qd, J = 8.9,6.5 Hz, 2H) AC92 640.9 ([M − H]⁻) 9.16 (d, J = 6.1 Hz, 1H), 7.65 (d, J =1.6 Hz, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.41 (m, 3H), 7.21 (t, J = 5.6Hz, 1H), 6.55 (d, J = 15.9 Hz, 1H), 6.41 (dd, J = 15.9, 7.8 Hz, 1H),4.59 (d, J = 5.6 Hz, 2H), 4.45 (qd, J = 9.0, 6.0 Hz, 2H), 4.12 (q, J =7.2 Hz, 1H) AC93 485.5 ([M + H]⁺) 7.52-7.41 (d, J = 8.2 Hz, ¹³C NMR (δ)³1H), 7.39-7.34 (m, 1H), 169.91, 7.24-7.17 (d, J = 1.8 Hz, 169.84, 2H),7.02-6.92 (m, 2H), 138.23, 6.90-6.83 (d, J = 11.4 Hz, 137.41, 1H), 6.71(br s, 1H), 136.84, 6.17 (br s, 1H), 134.79, 6.12-6.01 (dd, J = 11.4,10.3 Hz, 134.69, 1H), 4.44-4.38 (d, J = 4.2 Hz, 131.07, 1H), 128.69,4.35-4.27 (m, 1H), 4.10-3.99 (d, J = 5.1 Hz, 127.49, 2H), 127.43,2.78-2.67 (m, 1H), 2.44 (s, 3H), 126.72, 0.88-0.78 (m, 2H), 126.61 (q, J= 212.10 Hz), 0.60-0.45 (m, 2H) 125.61, 123.76, 47.89 (q, J = 28.28 Hz),43.46, 22.65, 19.97, 8.21 AC94 511.6 ([M]⁻) 8.36-8.24 (d, J = 2.4 Hz,3262, 1607, 1H), 7.75-7.64 (m, 1247, 1164, 1H), 7.38-7.24 (m, 1111 3H),7.24-7.09 (d, J = 1.8 Hz, 2H), 6.99-6.90 (m, 2H), 6.89-6.74 (d, J = 11.4Hz, 1H), 6.63-6.43 (m, 1H), 6.14-5.98 (m, 1H), 4.69-4.51 (d, J = 6.1 Hz,2H), 4.37-4.20 (m, 1H), 2.46-2.31 (s, 3H) AC95 48-61 626.9 ([M + H]⁺)7.58 (d, J = 7.9 Hz, 1H), 7.44-7.29 (m, 3H), 7.14 (dd, J = 7.9, 1.6 Hz,1H), 6.86 (d, J = 11.4 Hz, 1H), 6.76 (t, J = 5.9 Hz, 1H), 6.59 (br s,1H), 6.21-6.04 (m, 1H), 4.23 (d, J = 5.5 Hz, 1H), 3.98 (qd, J = 9.0, 6.5Hz, 2H) AC96 619.6 ([M + H]⁺) 8.83 (s, 1H), 8.06 (br, 1616, 1114 1H),7.90 (s, 2H), 7.63 (d, J = 8.1 Hz, 2H), 7.53 (m, 1H), 6.94 (m, 1H), 6.77(d, J = 15.3 Hz, 1H), 6.63 (d, J = 9.3 Hz, 1H), 4.84 (m, 1H), 4.30 (d, J= 5.6 Hz, 2H), 2.99 (s, 6H) AC97 606.6 ([M + H]⁺) 8.20 (d, J = 2.1 Hz,1644, 1113 1H), 7.73 (d, J = 2.7 Hz, 1H), 7.60 (m, 2H), 7.39 (s, 2H),7.29 (m, 1H), 6.79 (d, J = 8.4 Hz, 1H), 6.55 (d, J = 15.9 Hz, 1H), 6.40(m, 2H), 4.60 (d, J = 2.7 Hz, 2H), 4.13 (m, 1H), 3.95 (s, 3H) AC98577.87 ([M + H]⁺) 9.04 (t, J = 6.0 Hz, 1H), 1663, 1168 8.60 (t, J = 6.6Hz, 1H), 8.25 (s, 1H), 7.97 (d, J = 8.1 Hz, 1H), 7.87 (d, J = 6.3 Hz,2H), 7.69 (d, J = 7.5 Hz, 1H), 7.15 (dd, J = 15.9, 9.3 Hz, 1H), 6.89 (d,J = 15.9 Hz, 1H), 4.86 (m, 1H), 3.98 (m, 4H). AC99 574.81 ([M + H]⁺)8.69 (t, J = 6.0 Hz, 1H), 1650, 1164 8.58 (t, J = 6.6 Hz, 1H), 7.91 (s,1H), 7.85 (m, 1H), 7.61 (m, 2H), 7.52 (m, 2H), 6.98 (dd, J = 15.3, 9.0Hz, 1H), 6.76 (d, J = 15.3 Hz, 1H), 4.81 (m, 1H), 4.01 (m, 4H) AC100673.80 ([M + H]⁺) 8.29 (s, 1H), 8.22 (d, J = 8.1 Hz, 3403, 1659 1H),7.93 (d, J = 7.8 Hz, 1H), 7.72 (m, 1H), 7.65 (m, 2H), 7.40 (s, 2H), 7.18(br, 1H), 6.59 (d, J = 16.0 Hz, 1H), 6.43 (dd, J = 16.0, 7.6 Hz, 1H),5.02 (d, J = 1.2 Hz, 2H), 4.12 (m, 1H) AC101 636.83 ([M + H]⁺) 7.56 (d,J = 9.0 Hz, 1637, 1113 1H), 7.39 (d, J = 6.0 Hz, 2H), 7.26 (m, 2H), 6.54(d, J = 15.9 Hz, 1H), 6.37 (dd, J = 8.0, 15.9 Hz, 1H), 4.01 (m, 1H),3.84 (m, 2H), 3.33 (m, 2H), 3.04 (m, 2H), 2.84 (m, 3H), 2.62 (m, 1H)AC102 592.84 ([M + H]⁺) 7.60 (m, 2H), 7.32 (m, 1668, 1167 1H), 7.03 (d,J = 7.2 Hz, 2H), 6.74 (br, 1H), 6.62 (br, 1H), 6.56 (d, J = 16.2 Hz,1H), 6.41 (dd, J = 16.2, 7.8 Hz, 1H), 4.22 (d, J = 5.4 Hz, 2H), 4.14 (m,1H), 4.01 (m, 2H) AC103  99.2-105.0 612.7 ([M + H]⁺) 8.40 (d, J = 8.0Hz, 1H), 1634, 1113, 7.92 (d, J = 5.2 Hz, 1H), 809 7.59 (d, J = 8.0 Hz,1H), 7.35 (d, J = 8.0 Hz, 1H), 6.99 (dd, J = 16.0, 7.6 Hz, 1H), 6.76 (d,J = 16.0 Hz, 1H), 4.84 (m, 1H), 4.23 (d, J = 13.2 Hz, 1H), 3.97 (m, 1H),3.79 (d, J = 13.6 Hz, 1H), 3.16 (t, J = 11.2 Hz, 1H), 2.77 (t, J = 11.2Hz, 1H), 1.99 (s, 3H), 1.88 (m, 2H), 1.45 (m, 2H) AC104 680.97 ([M +H]⁺) 7.60 (m, 2H), 7.40 (m 3437, 3H), 6.55 (d, J = 15.6 Hz, 1644, 1H),6.41 (dd, J = 15.6, 1113, 7.8 Hz, 1H), 807, 4.24 (m, 1H), 3.34 (m, 2H),511 2.90 (m, 1H), 2.24 (m, 2H), 1.52 (m, 2H), 1.34 (m, 4H) AC105 609.9([M + H]⁺) 7.59 (s, 1H), 7.55 (m, 3303, 1649, 1H), 7.50 (m, 1H), 1115,2242, 7.40 (m, 2H), 6.54 (d, J = 16.0 Hz, 809, 506 1H), 6.50 (J = 16.0,8.0 Hz, 1H), 4.14 (m, 2H), 3.08 (m, 4H), 2.67 (m, 2H), 2.12 (m, 2H),1.70 (m, 2H). AC106 584.95 ([M + H]⁺) 7.59 (s, 1H), 7.51 (d, J = 8.4 Hz,3417, 1H), 7.40 (s, 1648, 2H), 7.36 (d, J = 6.8 Hz, 1112, 1H), 6.54 (d,J = 16.0 Hz, 805, 555 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 6.03 (d, J =8.0 Hz, 1H), 4.11 (m, 2H), 3.10 (m, 2H), 2.50 (m, 2H), 2.50 (s, 3H) (m,2H), 1.94 (m, 2H) AC107 609.9 ([M + H]⁺) 8.41 (d, J = 7.8 Hz, 1H), 3303,7.90 (s, 2H), 7.62 (m, 1645, 2H), 7.51 (m, 1H), 1115, 6.92 (dd, J =15.9, 9.0 Hz, 2243, 1H), 6.77 (d, J = 15.9 Hz, 810, 1H), 4.81 (m, 1H),507 3.73 (s, 2H), 3.31 (m, 1H), 3.28 (m, 1H), 2.82 (t, J = 11.4 Hz, 2H),2.82 (m, 2H), 2.30 (m, 2H), 1.88 (m, 2H), 1.57 (m, 2H) AC108 626.9 ([M +H]⁺) 7.60 (m, 2H) 7.39 (s, 3420, 2H), 7.28 (m, 1H), 1649, 6.56 (d, J =15.6 Hz, 1H), 1113, 6.40 (dd, J = 15.6, 7.8 Hz, 809, 1H), 5.91 (m, 1H),554 4.65 (m, 2H), 4.10 (m, 1H), 4.07 (m, 2H), 3.59 (m, 1H), 2.74 (m,2H), 2.13 (m, 4H), 2.07 (m, 1H) AC109 614.6 ([M + H]⁺) 7.56 (m, 2H),7.39 (s, 1647, 1113 2H), 7.29 (s, 1H), 6.50 (d, J = 15.9 Hz, 1H), 6.41(dd, J = 15.9, 8.0 Hz 1H), 4.09 (m, 1H), 3.88 (m, 2H), 3.49 (m, 2H),2.92 (m, 2H), 2.81 (m, 1H), 2.74 (m, 2H), 2.25 (m, 4H) AC110 572.6 ([M +H]⁺) 11.20 (s, 1H), 8.66 (br, 3412, 1690, 1H), 7.92 (m, 3H), 1114, 846,7.62 (d, J = 8.0 Hz, 1H), 559 7.45 (d, J = 8.0 Hz, 1H), 6.77 (dd, J =15.6, 9.2 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.85 (m, 1H), 3.74 (d, J =5.2 Hz, 2H), 3.61 (s, 3H) AC111 582.79 ([M + H]⁺) 8.63 (t, J = 6.0 Hz,1H), 3419, 1659, 8.04 (t, J = 6.0 Hz, 1H), 843, 557 7.92 (m, 3H), 7.62(d, J = 1.2 Hz, 1H), 7.47 (d, J = 7.6 Hz, 1H), 7.00 (dd, J = 15.6, 8.8Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 5.19 (d, J = 1.6 Hz, 1H), 5.01 (d, J= 1.2 Hz, 1H), 4.85 (m, 1H), 3.86 (d, J = 5.6 Hz, 2H), 3.75 (t, J = 5.6Hz, 2H) AC112 582.79 ([M + H]⁺) 8.84 (br, 1H), 8.58 (m, 3399, 1662, 1H),8.30 (m, 1H), 1114, 807, 7.91 (s, 2H), 7.61 (d, J = 8.1 Hz, 582 1H),7.42 (d, J = 7.8 Hz, 1H), 7.00 (dd, J = 15.6, 9.3 Hz, 1H), 6.77 (d, J =15.6 Hz, 1H), 4.85 (m, 1H), 4.11 (d, J = 5.6 Hz, 1H), 3.73 (d, J = 5.6Hz, 1H), 3.04 (s, 6H) AC113 626.88 ([M + H]⁺) 8.48 (t, J = 5.2 Hz, 1H),3431, 1651, 8.3 (s, 1H), 7.90 (s, 2H), 1113, 808, 7.79 (dd, J = 2.0, 2.0Hz 554 2H), 7.58 (d, J = 8.4 Hz, 1H) 7.46 (d, J = 7.6 Hz, 1H) 7.26 (d, J= 7.6 Hz, 1H), 6.98 (m, 1H), 6.75 (d, J = 15.6 Hz, 1H), 4.85 (m, 1H),3.49 (d, J = 6.4 Hz, 2H) 2.87 (t, J = 6.4 Hz, 2H) AC114 113.7-117.5570.7 ([M + H]⁺) 8.77 (s, 1H), 8.58 (d, J = 7.2 Hz, 2H), 7.93 (d, J =7.2 Hz, 2H), 7.60 (dd, J = 1.2, 0.8 Hz, 1H), 7.37 (d, J = 7.6 Hz, 1H),6.99 (m, 1H), 6.77 (d, J = 16 Hz, 1H), 4.85 (m, 1H), 4.10 (m, 1H) 3.29(m, 2H), 3.05 (m, 2H), 2.0 (m, 2H), 1.76 (m, 2H) AC115 529.00 ([M + H]⁺)8.43 (s, 1H), 7.79 (d, J = 8.0 Hz, 1589, 3459, 1H), 7.51 (m, 801, 11101H), 7.36 (d, J = 8.4 Hz, 3H), 7.21 (m, 3H), 6.55 (d, J = 15.6 Hz, 1H),6.36 (dd, J = 15.6, 8.0 Hz, 1H), 5.04 (d, J = 5.6 Hz, 2H), 4.10 (m, 1H),2.35 (s, 3H) AC116 614.87 ([M + H]⁺) 7.99 (d, J = 8.4 Hz, 1H), 3424,1657, 7.46 (d, J = 1.6 Hz, 1H), 1165 7.34 (d, J = 6.4 Hz, 2H), 7.28 (m,2H), 6.62 (m, 2H), 6.47 (dd, J = 16.0, 7.2 Hz, 1H), 4.23 (m, 2H), 4.12(m, 1H), 4.00 (m, 2H) AC117 525.42 ([M − H]⁻) 8.39 (br, 1H), 7.85 (br,3401, 1636, 1H), 7.62 (m, 3H), 1113, 750 7.53 (d, J = 8.0 Hz, 1H), 7.46(s, 1H), 7.40 (d, J = 8.0 Hz, 1H), 7.17 (m, 1H), 6.78 (dd, J = 16.0, 8.8Hz, 1H), 6.70 (m, 1H), 4.77 (m, 1H), 4.66 (s, 1H), 4.32 (s, 1H), 2.97(s, 3H), 2.16 (s, 3H) AC118 471.79 ([M + H]⁺) 7.36 (d, J = 8.0 Hz, 2H),3437, 1655, 7.27 (m, 2H), 7.22 (m, 1262, 1105, 2H), 6.57 (d, J = 16.0Hz, 802 1H), 6.38 (dd, J = 16.0, 8.0 Hz, 1H), 6.10 (br, 1H), 4.15 (m,2H), 3.89 (m, 1H), 3.80 (m, 2H), 3.35 (m, 1H), 2.46 (s, 3H), 2.06 (s,1H), 1.96 (m, 2H), 1.65 (m, 1H) BC1 492.17 ([M + H]⁺) 7.39 (s, 2H),3211, 1569, 7.25-7.18 (m, 3H), 6.58 (d, J = 16.0 Hz, 1113, 806 1H), 6.30(dd, J = 16.0, 8.4 Hz, 1H), 5.91-5.70 (br, 2H), 4.05 (m, 1H), 3.05-2.80(m, 6H), 2.70 (m, 1H), 1.81 (m, 1H) BC2 506.4 ([M + H]⁺) 8.80 (s, 1H),8.20 (s, 2923, 1542, 1H), 7.82 (m, 3H), 1033, 805 7.4 (s, 2H), 6.62 (d,J = 16.0 Hz, 1H), 6.52 (dd, J = 16.0, 8.0 Hz, 1H), 4.18 (m, 1H), 3.38(m, 2H), 2.98 (m, 2H), 2.71 (m, 1H), 2.04 (m, 2H), 1.54 (s, 3H). BC3518.04 ([M − H]⁻) 7.40 (s, 2H), 3120, 1592, 7.33-7.22 (m, 3H), 6.61 (d,J = 16.0 Hz, 1146, 895 1H), 6.34-6.28 (dd, J = 16.0, 8.0 Hz, 1H),5.96-5.80 (m, 3H), 5.22 (m, 4H), 4.01 (m, 2H), 2.84-2.99 (m, 2H), 2.71(m, 1H), 1.86 (m, 1H) BC4 529.02 ([M + H]⁺) 7.39 (s, 2H), 3283, 1652,7.25-7.20 (m, 3H), 6.34 (d, J = 16.0 Hz, 1241, 811 1H), 6.30 (dd, J =16.0, 8.0 Hz, 1H), 5.81 (br, 1H), 5.48 (m, 1H), 4.10 (m, 1H), 3.10 (m,2H), 2.86-3.07 (m, 2H), 2.86 (m, 1H), 1.81 (m, 1H); BC5 544.25 ([M −H]⁻) 7.40 (s, 2H), 7.21 (s, 3489, 3291, 1H), 7.12 (m, 1H), 1655, 1112,6.56 (d, J = 16.0 Hz, 1H), 808 6.32 (dd, J = 16.0, 8.4 Hz, 1H), 5.85 (brs, 1H), 5.23 (br s, 1H), 4.12 (m, 1H), 3.18 (m, 3H), 2.80 (m, 3H), 2.08(m, 2H), 1.83 (m, 5H), 1.25 (m, 2H), 1.01 (m, 3H), 0.78 (m, 2H) BC6485.96 ([M − H]⁻) 7.40 (s, 2H), 3429, 1114, 7.31-7.18 (m, 3H), 6.58 (d,J = 16.0 Hz, 804 1H), 6.24-6.28 (dd, J = 16.0, 8.0 Hz, 1H), 5.40 (br,1H), 4.01 (m, 2H), 2.78-3.01 (m, 2H), 2.51 (s, 1H), 1.86 (m, 1H), 1.20(m, 2H), 1.01 (m, 2H), 0.78 (m, 2H) BC7 500.01 ([M − H]⁻) 7.40 (s, 2H),7.31 (s, 3296, 1115, 1H), 7.18 (m, 1H), 806 7.18 (s, 1H), 6.58 (d, J =16.0 Hz, 1H), 6.32 (dd, J = 16.0, 8.0 Hz, 1H), 5.78 (br s, 1H), 5.21 (brs, 1H), 4.01 (m, 1H), 2.78 (m, 2H), 2.01 (m, 1H), 1.86 (m, 4H), 1.25 (m,2H), 1.01 (m, 3H), 0.78 (m, 2H) BC8 511.88 ([M − H]⁻) 7.38-7.20 (m, 5H),1657, 1113, 6.62 (d, J = 16.0 Hz, 1H), 855 6.34 (dd, J = 16.0, 8.0 Hz,1H), 5.83 (br, 1H), 5.52 (m, 1H), 4.12 (m, 1H), 3.12 (m, 2H), 3.06-2.82(m, 2H), 2.75 (m, 1H), 1.85 (m, 1H) BC9 179-181 556.83 ([M − H]⁻) 8.30(s, 1H), 7.68 (d, J = 6.4 Hz, 1H), 7.38-7.20 (m, 5H), 6.60 (d, J = 16.0Hz, 1H), 6.34 (dd, J = 16.0, 8.0 Hz, 1H), 5.63 (br, 1H), 5.52 (m, 1H),4.12 (m, 1H), 3.56 (s, 2H), 3.06-2.82 (m, 2H), 2.70 (m, 1H), 1.82 (m,1H) BC10 497.98 ([M − H]⁻) 7.38-7.20 (m, 5H), 3027, 1654, 6.62 (d, J =16.0 Hz, 1H), 815 6.34 (dd, J = 16.0, 8.0 Hz, 1H), 5.83 (br, 1H), 5.52(m, 1H), 4.12 (m, 1H), 3.02 (m, 3H), 2.82 (m, 1H), 2.50 (m, 3H), 1.82(m, 1H), 1.42 (m, 1H) BC11 530.09 ([M − H]⁻) 7.80 (m, 1H), 7.48 (m,1715, 1113, 2H), 7.32 6.65 (d, J = 16.0 Hz, 816 1H), 6.54 (dd, J = 16.0,8.0 Hz, 1H), 5.38 (m, 1H), 4.18 (m, 1H), 3.62 (m, 1H), 3.32 (m, 1H),2.86 (m, 1H), 1.81 (m, 1H) BC12 514.86 ([M + H]⁺) 7.32, (d, J = 6.0 Hz,2H) 3428, 1112, 7.28 (m, 1H), 7.20 (d, J = 8.0, 857 1H), 7.14 (d, J =8.8, 1H), 6.70 (d, J = 8.0 Hz, 1H), 6.60 (m, 2H), 4.15 (m, 1H), 3.85 (m,1H), 3.65 (m, 1H), 3.46 (m, 2H), 3.19 (m, 2H); BC13 121-126 553.06 ([M −H]⁻) 8.33 (br, 1H), 7.59 (s, 1H), 7.45 (m, 3H), 6.72 (d, J = 3.6, 1H),6.39 (m, 1H), 4.71 (t, J = 7.2 Hz, 2H), 4.15 (m, 2H) BC14 172-175 554.0([M − H]⁻) 8.83 (t, J = 6.6 Hz, 1H), 8.42 (t, J = 14.7 Hz, 1H), 8.22 (d,J = 8.1 Hz, 1H), 8.13 (t, J = 6.3 Hz, 1H), 7.98-7.86 (m, 2H), 7.16-7.07(m, 1H), 7.01-6.93 (m, 1H), 4.96-4.81 (m, 3H), 4.00-3.88 (m, 2H) CC1107-109 402.00 ([M + H]⁺) 7.37 (m, 3H), 7.28 (m, 4H), 6.60 (d, J = 16.0Hz, 1H), 6.36 (dd, J = 16.0, 8.0 Hz, 1H), 5.75 (br s, 1H), 4.46 (d, J =6 Hz, 2H), 4.01 (m, 1H), 2.11 (s, 3H) CC2 118-120 428.11 ([M + H]⁺) 7.37(m, 3H), 7.28 (m, 4H), 6.60 (d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0,8.0 Hz, 1H), 5.83 (br s, 1H), 4.46 (d, J = 6.0 Hz, 2H), 4.11 (m, 1H),1.40 (m, 1H), 1.02 (m, 2H), 0.77 (m, 2H) CC3 119-122 468.20 ([M − H]⁻)7.38 (m, 3H), 7.27 (m, 3H), 6.60 (d, J = 16.0 Hz, 1H), 6.36 (dd, J =16.0, 8.4 Hz, 1H), 5.00 (br s, 1H), 4.48 (d, J = 5.6 Hz, 2H), 4.11 (m,1H), 3.15 (q, J = 10.4 Hz, 2H) CC4 414.16 ([M − H]⁻) 7.37 (m, 3H), 7.28(m, 3H), 6.60 (d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H),5.69 (br s, 1H), 4.46 (d, J = 6.0 Hz, 2H), 4.21 (m, 1H), 2.29 (q, J =5.8 Hz, 2H), 1.30 (t, J = 7.2 Hz, 3H) CC5 460.28 ([M − H]⁻) 7.40 (m,3H), 7.28 (m, 2H), 6.60 (d, J = 15.6 Hz, 1H), 6.33 (dd, J = 15.6, 8.0Hz, 1H), 5.84 (br s, 1H), 4.46 (d, J = 5.6 Hz, 2H), 4.10 (m, 1H), 1.36(m, 1H), 1.02 (m, 2H), 0.77 (m, 2H) CC6 106-108 504.08 ([M − H]⁻) 7.40(m, 3H), 7.26 (m, 1H), 6.60 (d, J = 16.0 Hz, 1H), 6.34 (dd, J = 16.0,8.0 Hz, 1H), 5.96 (br s, 1H), 4.49 (d, J = 5.6 Hz, 2H), 4.10 (m, 1H),3.15 (q, J = 10.8 Hz, 2H) CC7 127-128 436.03 ([M + H]⁺) 7.42 (m, 4H),7.24 (m, 2H), 6.53 (d, J = 16.0 Hz, 1H), 6.36 (dd, J = 16.0, 8.0 Hz,1H), 5.86 (br s, 1H), 4.51 (d, J = 6.0 Hz, 2H), 4.05 (m, 1H), 2.02 (s,3H) CC8 129-131 462.15 ([M + H]⁺) 8.58 (t, J = 5.6 Hz, 1H), 7.72 (m,1H), 7.66 (m, 3H), 7.49 (d, J = 8.0 Hz, 1H), 7.30 (d, J = 8.0 Hz, 1H),6.90 (dd, J = 16.0, 8.0 Hz, 1H), 6.73 (d, J = 16 Hz, 1H), 4.81 (m, 1H),4.33 (d, J = 6.0 Hz, 1H), 1.64 (m, 1H), 0.68 (m, 4H) CC9 132-134 504.25([M + H]⁺) 7.41 (m, 3H), 7.26 (m, 3H), 6.54 (d, J = 16.0 Hz, 1H), 6.37(dd, J = 16.0, 8.0 Hz, 1H), 6.13 (br s, 1H), 4.56 (d, J = 6.0 Hz, 2H),4.11 (m, 1H), 3.13 (m, 2H) CC10 538.03 ([M + 2H]⁺) 7.38 (m, 4H), 6.56(d, J = 16.0 Hz, 1651, 1112, 1H), 807 6.38 (dd, J = 16.0, 8.0 Hz, 1H),6.18 (m, 1H), 4.58 (m, 2H), 4.08 (m, 1H), 3.08 (m, 2H) CC11 111-112494.12 ([M − H]⁻) 7.42 (m, 3H), 7.24 (m, 1H), 6.54 (d, J = 15.6 Hz, 1H),6.34 (dd, J = 16.0, 8.0 Hz, 1H), 6.03 (m, 1H), 4.53 (d, J = 6.0 Hz, 1H),4.10 (m, 1H), 1.39 (m, 1H), 1.00 (m, 2H), 0.77 (m, 2H) CC12 76-78 510.07([M − H]⁻) 7.39 (s, 4H), 7.34 (d, J = 8.0 Hz, 1H), 7.26 (m, 1H), 6.57(d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 6.10 (br s, 1H),4.49 (d, J = 6.0 Hz, 2H), 4.10 (m, 1H), 1.20 (s, 9H) CC13 73-76 563.37([M − H]⁻) 8.51 (d, J = 5.2 Hz, 1H), 7.63 (s, 1H), 7.51 (m, 1H), 7.45(m, 2H), 7.39 (s, 2H), 7.28 (m, 1H), 6.58 (m, 2H), 6.37 (dd, J = 16.0,8.0 Hz, 1H), 4.71 (d, J = 6.0 Hz, 1H), 4.11 (m, 1H) CC14 581.45 ([M +1H]⁺) 8.51 (m, 1H), 8.30 (d, J = 2.4 Hz, 3430, 1656, 1H), 7.73 (m, 1109,806 1H), 7.61 (s, 2H), 7.51 (s, 1H), 7.32 (m, 3H), 6.66 (d, J = 16.0 Hz,1H), 6.56 (dd, J = 16.0, 8.4 Hz, 1H), 4.50 (m, 1H), 4.45 (d, J = 5.6 Hz,1H), 3.56 (s, 2H) CC15 480.24 ([M + H]⁺) 7.40 (m, 3H), 7.33 (m, 3293,1651, 1H), 7.22 (m, 2H), 1543, 1114, 6.54 (d, J = 15.6 Hz, 1H), 812 6.34(dd, J = 16.0, 8.0 Hz, 1H), 6.03 (br s, 1H), 4.53 (d, J = 6.0 Hz, 2H),4.13 (m, 1H), 1.41 (m, 1H), 1.00 (m, 2H), 0.77 (m, 2H) CC16 520.33 ([M −H]⁻) 7.42 (s, 1H), 7.37 (m, 3307, 1665, 3H), 7.22 (m, 1H), 1114, 8136.54 (d, J = 16.0 Hz, 1H), 6.36 (dd, J = 16.0, 8.0 Hz, 1H), 6.19 (br s,1H), 4.51 (d, J = 6.0 Hz, 2H), 4.21 (m, 1H), 3.33 (m, 2H) CC17 117-119459.83 ([M − H]⁻) 7.51 (m, 2H), 7.39 (m, 3293, 1633, 2H), 7.24 (m, 2H),1110, 820 6.52 (d, J = 15.6 Hz, 1H), 6.38 (dd, J = 15.6, 7.6 Hz, 1H),6.02 (br s, 1H), 4.53 (d, J = 6.0 Hz, 2H), 4.14 (m, 1H), 1.38 (m, 1H)),1.00 (m, 2H), 0.77 (m, 2H) CC18 119-123 501.88 ([M − H]⁻) 7.48 (m, 2H),7.41 (s, 3435, 1644, 1H), 7.36 (d, J = 8.0 Hz, 1111, 817 1H), 7.23 (m,2H), 6.52 (d, J = 16.0 Hz, 1H), 6.39 (dd, J = 16.0, 8.0 Hz, 1H), 6.13(br s, 1H), 4.56 (d, J = 6.0 Hz, 2H), 4.15 (m, 1H), 3.13 (m, 2H) CC19530 ([M + H]⁺) 7.41 (m, 2H), 7.24 (m, 3435, 1644, 1H), 6.53 (d, J = 16.0Hz, 1111, 817 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 4.53 (m, 2H), 4.10(m, 1H), 3.42 (m, 2H), 2.97 (s, 3H), 2.78 (m, 2H) CC20 512 ([M + H]⁺)7.42 (m, 3H), 7.24 (m, 3293, 1633, 1H), 6.54 (d, J = 15.6 Hz, 1110, 8201H), 6.34 (dd, J = 15.6, 8.0 Hz, 1H), 6.03 (m 1H), 4.53 (d, J = 6.0 Hz,1H), 4.10 (m, 1H), 1.19 (m, 1H), 1.00 (m, 2H), 0.77 (m, 2H) CC21 55-58493.99 ([M − H]⁻) (DMSO-d₆) 8.62 (m, 1H), 7.95 (s, 1H), 7.85 (m, 1H),7.66 (m, 3H), 7.47 (d, J = 8.0 Hz, 1H), 6.98 (dd, J = 16.0, 8.0 Hz, 1H),6.84 (d, J = 16.0 Hz, 1H), 4.83 (m, 1H), 4.44 (s, 2H), 1.68 (m, 1H),0.71 (m, 4H) CC22 67-69 530.01 ([M + H]⁺) 8.62 (m, 1H), 7.90 (s, 3H),7.82 (m, 1H), 7.45 (m, 1H), 6.98 (m, 1H), 6.84 (d, J = 16.0 Hz, 1H),4.82 (m, 1H), 4.4 (s, 2H), 1.66 (m, 1H), 0.72 (m, 4H) CC23 69-71 564.99([M − H]⁻) 9.02 (br s, 1H), 8.54 (br s, 1H), 8.26 (br s, 1H), 7.48-7.54(m, 3H), 7.22-7.42 (m, 3H), 6.59-6.62 (m, 2H), 6.38-6.42 (m, 1H), 4.82(m, 2H), 4.19 (s, 1H) CC24 125-127 570.26 ([M − H]⁻) 7.64 (s, 1H), 7.54(s, 2H), 7.46 (s, 2H), 6.62 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0,8.4 Hz, 1H), 6.03 (m, 1H), 4.65 (d, J = 6.4 Hz, 2H), 4.14 (m, 1H,), 3.13(q, J = 10.6 Hz, 2H) CC25 579.86 ([M − H]⁻) 7.60 (s, 1H), 7.40 (s, 3297,1663, 2H), 7.37 (d, J = 8.0 Hz, 1114, 809 1H), 7.31 (d, J = 8.0 Hz, 1H),6.53 (d, 1H, J = 16.0 Hz), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 6.17 (br s,1H), 4.56 (d, J = 6.4 Hz, 2H), 4.12 (m, 1H), 3.15 (q, J = 10.6 Hz, 2H)CC26 129-131 539.89 ([M + H]⁺) 7.59 (s, 1H), 7.39 (m, 2H), 7.30 (s, 1H),6.53 (d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 6.06 (br s,1H), 4.42 (d, J = 4.4 Hz, 2H), 4.12 (m, 1H), 1.35 (br s, 1H), 0.95 (brs, 2H), 0.75 (m, 2H) CC27 519.95 ([M − H]⁻) 7.39 (s, 2H), 7.33 (t, J =7.6 Hz, 3306, 1786 1H), 7.14 (m, 2H), 6.56 (d, J = 16.0 Hz, 1H), 6.35(dd, J = 16.0, 7.6 Hz, 1H), 6.06 (br s, 1H), 4.52 (d, J = 16.0 Hz, 2H),4.08 (m, 1H), 3.90 (s, 2H), 3.13 (m, 2H) CC28 477.93 ([M − H]⁻) 7.39 (s,2H), 7.35 (m, 3625, 1747 1H), 7.14 (m, 2H), 6.55 (d, J = 15.6 Hz, 1H),6.33 (dd, J = 15.6, 8.0 Hz, 1H), 5.93 (br s, 1H), 4.49 (d, J = 16.0 Hz,2H), 4.10 (m, 1H), 1.36 (m, 1H), 1.00 (m, 2H), 0.77 (m, 2H) CC29 620.86([M − H]⁻) 8.58 (d, J = 4.6 Hz, 1H), 1645, 1115, 7.74 (m, 1H), 7.62 (m,808 2H), 7.52 (m, 1H), 7.4 (s, 2H), 7.3 (m, 1H), 7.2 (m, 2H), 6.60 (d, J= 16.0 Hz, 1H), 6.38 (dd, J = 16.0, 8.0 Hz, 1H), 5.02 (s, 1H), 4.8 (s,1H), 4.8 (d, J = 10 Hz, 2H), 4.10 (m, 1H), 1.8 (m, 1H), 1.2 (m, 2H), 0.6(m, 2H) CC30 101-104 559.75 ([M − H]⁻) 7.41 (m, 4H), 7.24 (m, 1H), 6.53(d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 6.12 (br s, 1H),4.53 (m, 2H), 4.10 (m, 1H), 3.42 (m, 2H), 2.91 (s, 3H), 2.78 (m, 2H)CC31 177-178 463 ([M − H]⁻) 7.58 (m, 2H), 7.41 (m, 3H), 7.24 (m, 1H),6.53 (d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 4.70 (br s,1H), 4.43 (s, 2H), 4.08 (m, 1H), 3.21 (m, 2H), 1.25 (m, 3H); CC32141-142 532.99 ([M + H]⁺) 7.66 (m, 2H), 7.54 (m, 1H), 7.41 (s, 2H), 6.62(d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 4.59 (s, 3H),4.19 (m, 1H), 3.25 (m, 2H), 1.15 (m, 2H) CC33 540.88 ([M − H]⁻) 7.57 (s,1H), 7.40 (m, 3338, 1631, 2H), 7.30 (s, 1H), 1578, 1114, 7.20 (br s,1H), 6.53 (d, J = 16.0 Hz, 809 1H), 6.33 (dd, J = 16.0, 8.0 Hz, 1H),6.06 (br s, 1H), 4.75 (br s, 1H), 4.42 (s, 2H), 4.20 (br s, 1H), 4.15(m, 2H), 3.20 (m, 2H), 1.15 (m, 3H) CC34 118-120 541.40 ([M + H]⁺) 7.42(m, 3H), 7.28 (m, 2H), 6.54 (d, J = 16.0 Hz, 1H), 6.36 (dd, J = 16.0,8.0 Hz, 1H), 4.96 (m, 1H), 4.51 (d, J = 5.6 Hz, 2H), 4.12 (m, 1H), 3.69(t, J = 4.8 Hz, 4H), 3.35 (t, J = 4.8 Hz, 1H) CC35 78-79 547.82 ([M +H]⁺) 9.95 (br s, 1H), 8.17 (d, J = 4.8 Hz, 1H), 7.61 (d, J = 6.4 Hz),7.43 (m, 3H), 7.24 (m, 2H), 6.90 (t, J = 5.6 Hz, 1H), 6.66 (d, J = 8.4Hz, 1H), 6.54 (d, J = 16.0 Hz, 1H), 6.33 (dd, J = 16.0, 8.0 Hz, 1H),4.65 (d, J = 6.0 Hz, 1H), 4.09 (m, 1H) CC36 497 ([M − H]⁻) 7.39 (m, 4H),7.28 (m, 3350, 1705, 1H), 6.54 (d, J = 16.0 Hz, 1114, 808 1H), 6.34 (dd,J = 16.0, 8.0 Hz, 1H), 4.97 (br s, 1H), 4.38 (d, J = 6.0 Hz, 2H), 4.10(m, 1H), 2.9 (s, 3H), 2.7 (s, 3H) CC37 88-91 515.01 ([M + H]⁺) 7.49 (d,J = 8 Hz, 1H), 7.41 (d, J = 7.2 Hz, 2H), 7.26 (m, 2H), 6.50 (d, J = 16Hz, 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 6.0 (brs, 1H), 5.73 (br s,1H), 4.80 (br s, 2H), 4.09 (m, 1H), 1.23 (m, 3H) CC38 63-66 526.97 ([M +H]⁺) 7.48 (d, J = 8 Hz, 1H), 7.39 (m, 3H), 7.27 (m, 1H), 6.54 (d, J = 16Hz, 1H), 6.33 (dd, J = 6.0, 8.0 Hz, 1H), 6.17 (br s, 1H), 5.92 (br s,1H), 5.83 (m, 2H), 5.29 (t, J = 15.4 Hz, 2H), 4.80 (br s, 2H), 4.12 (m,1H), 4.02 (br s, 2H) CC39 526.09 ([M − H]⁻) 7.39 (m, 4H), 7.28 (m, 3350,1705, 1H), 6.54 (d, J = 16.0 Hz, 1114, 808 1H), 6.34 (dd, J = 16.0, 8.0Hz, 1H), 4.97 (br s, 1H), 4.38 (d, J = 6.0 Hz, 2H), 4.10 (m, 1H), 1.53(s, 9H) CC40 159-160 580.25 ([M − H]⁻) 7.46 (m, 5H), 7.29 (m, 1H), 7.20(m, 3H), 6.55 (d, J = 16.0 Hz, 1H), 6.37 (dd, J = 16.0, 8.0 Hz, 1H),5.62 (br s, 1H), 4.55 (d, J = 6.4 Hz, 2H), 4.11 (m, 1H) CC41 512.22 ([M− H]⁻) 7.48 (m, 1H), 7.43 (m, 1740, 1701, 3H), 7.38 (m, 1H), 1114, 8087.23 (s, 1H), 6.55 (d, J = 16.0 Hz, 1H), 6.36 (d, J = 16.0 Hz, 1H), 4.60(d, 2H), 4.18 (m, 1H), 3.85 (s, 3H) CC42 161-163 578.96 ([M − H]⁻)(DMSO-d₆) 9.45 (br s, 2H), 7.90 (s, 2H), 7.75 (s, 1H), 7.46 (br s, 1H),7.28 (br s, 1H), 6.93 (m, 1H), 6.75 (br s, 1H), 4.80 (m, 1H), 4.40 (brs, 2H), 3.90 (br s, 2H) CC43 140-142 505.39 ([M + H]⁺) 8.11 (d, J = 4.0Hz, 1H), 7.40 (m, 5H), 7.22 (m, 1H), 6.61 (m, 2H), 6.35 (m, 2H), 4.94(br s, 1H) 4.61 (d, J = 6.4 Hz, 2H), 4.11 (m, 1H) CC44 536.88 ([M − H]⁻)8.41 (s, 1H), 7.77 (s, 3320, 1674, 1H), 7.47 (br s, 1H), 1114, 808 7.40(s, 2H), 6.58 (d, J = 16.0 Hz, 1H), 6.45 (dd, J = 16.0, 8.0 Hz, 1H),4.68 (d, J = 4.0 Hz, 2H), 4.14 (m, 1H), 3.24 (q, J = 10.8 Hz, 2H) CC45494.88 ([M − H]⁻) 8.41 (s, 1H), 7.76 (s, 3309, 1659, 1H), 7.40 (s, 2H),1115, 808 7.15 (br s, 1H), 6.58 (d, J = 16.0 Hz, 1H), 6.44 (dd, J =16.0, 8.0 Hz, 1H), 4.67 (d, J = 4.4 Hz, 2H), 4.16 (m, 1H), 1.57 (m, 1H),1.04 (m, 2H), 0.87 (m, 2H) CC46 151-153 554.04 ([M − H]⁻) 8.06 (m, 1H),7.61 (m, 4H), 7.48 (s, 2H), 7.44 (d, J = 8.0 Hz, 1H), 7.38 (m, 1H), 6.42(m, 1H), 5.92 (br s, 1H), 4.92 (m, 2H), 4.24 (m, 1H), 3.12 (m, 2H) CC47478.09 ([M + H]⁺) 8.06 (m, 2H), 7.61 (m, 3309, 1659, 4H), 7.48 (s, 2H),1115, 808 7.44 (d, J = 8.0 Hz, 1H), 7.38 (m, 2H), 6.42 (m, 1H), 4.92 (s,2H), 1.36 (m, 1H), 1.00 (m, 2H), 0.77 (m, 2H) CC48 511.05 ([M + H]⁺)8.06 (m, 2H), 7.61 (m, 3309, 1659, 3H), 7.48 (s, 2H), 1115, 808 7.44 (d,J = 8.0 Hz, 1H), 7.38 (m, 2H), 6.42 (m, 1H), 4.92 (s, 2H), 1.36 (m, 1H),1.00 (m, 2H), 0.77 (m, 2H) CC49 84-87 515.33 ([M + H]⁺). 8.06 (m, 1H),7.98 (m, 1H), 7.61 (m, 3H), 7.48 (s, 2H), 7.44 (d, J = 8.0 Hz, 1H), 7.38(m, 2H), 6.42 (m, 1H), 4.92 (s, 2H), 4.6 (br s, 1H), 4.24 (m, 1H), 3.21(m, 2H), 1.2 (t, J = 4.6 Hz, 3H) CC50 138-140 461.32 ([M − 1H]⁻) 9.81(s, 1H), 7.90 (s, 1H), 7.84 (s, 2H), 7.34 (d, J = 8.4 Hz, 2H), 6.65 (d,J = 15.6 Hz, 1H), 6.61 (m, 1H), 6.57 (s, 1H), 6.48 (dd, J = 15.6, 8.8Hz, 1H), 4.74 (m, 1H), 1.64 (m, 1H), 0.75 (m, 4H); CC51 149-150 505.31([M − H]⁻) 7.56 (br s, 1H), 7.4 (s, 3H), 7.3 (m, 3H), 7.05 (br s, 1H),6.8 (d, J = 6 Hz, 2H), 6.57 (m, 2H), 6.20 (m, 2H), 4.05 (m, 1H), 3.2 (q,J = 10.4 Hz, 2H) CC52 464.87 ([M − H]⁻) 7.40 (s, 2H), 7.18 (s, 3309,1659, 1H), 7.08 (s, 1H), 1115, 808 6.85 (m, 1H), 6.45 (m, 1H), 6.20 (m,1H), 5.55 (s, 1H), 4.08 (m, 1H), 1.30-1.10 (m, 4H), 1.90 (m, 1H) CC53506 ([M + H]⁺) 7.40 (s, 2H), 7.18 (s, 3309, 1659, 1H), 7.08 (s, 1H),1115, 808 6.85 (m, 1H), 6.45 (m, 1H), 6.20 (m, 1H), 5.55 (s, 1H), 4.08(m, 1H), 3.21 (m, 2H) CC54 504 ([M + H]⁺) 7.28 (s, 2H), 7.25 (m, 2H),7.10 (d, J = 8.0 Hz, 2H), 6.89 (d, J = 11.4 Hz, 1H), 6.07 (br s, 1H),6.01 (m, 1H), 4.51 (d, J = 5.8 Hz, 2H), 4.34 (m, 1H), 3.12 (q, J = 7.5Hz, 2H) DC1 93-97 398.05 ([M + H]⁺) 8.56 (s, 1H), 8.11 (s, 1H), 7.68 (d,J = 8.4 Hz, 2H), 7.54 (d, J = 8.4 Hz, 2H), 7.38 (t, J = 1.8 Hz, 1H),7.29 (s, 2H), 6.62 (d, J = 15.6 Hz, 1H), 6.42 (dd, J = 15.6, 8.2 Hz,1H), 4.15 (m, 1H) DC2 363.0746 (363.075) 8.59 (s, 1H), 8.13 (s, 3121,1524, 1H), 7.69 (d, J = 8.5 Hz, 1251, 1165, 2H), 7.55 (d, J = 8.5 Hz,1119 2H), 7.41-7.29 (m, 4H), 6.64 (d, J = 15.7 Hz, 1H), 6.47 (dd, J =15.9, 8.0 Hz, 1H), 4.17 (m, 1H) DC3 329.1144 (329.114) 8.56 (s, 1H),8.11 (s, 1521, 1246, 1H), 7.65 (d, J = 8.4 Hz, 1219, 1162, 2H), 7.52 (d,J = 8.3 Hz, 1152, 1107 2H), 7.40 (m, 5H), 6.61 (d, J = 15.8 Hz, 1H),6.51 (dd, J = 15.9, 7.7 Hz, 1H), 4.18 (m, 1H) DC4 364.11 ([M + H]⁺) 8.56(s, 1H), 8.10 (s, 3147, 1528, 1H), 7.66 (d, J = 2.0 Hz, 1494, 1246, 2H),7.52 (d, J = 8.8 Hz, 1165, 1108 2H), 7.38 (d, J = 2.4 Hz, 2H), 7.34 (d,J = 8.4 Hz, 2H), 6.61 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 7.6 Hz,1H), 4.15 (m, 1H) DC5 344.25 ([M + H]⁺) 8.54 (s, 1H), 8.10 (s, 3122,3047, 1H), 7.62 (d, J = 8.3 Hz, 1523, 1252, 2H), 7.50 (d, J = 8.4 Hz,1160, 1107 2H), 7.25 (d, J = 8.3 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 6.60(d, J = 16.0 Hz, 1H), 6.51 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H),2.37 (s, 3H) DC6 360.28 ([M + H]⁺) 8.55 (s, 1H), 8.10 (s, 3124, 2936,1H), 7.65 (d, J = 8.8 Hz, 1522, 1249, 2H), 7.52 (d, J = 8.8 Hz, 11602H), 7.32 (d, J = 8.8 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 6.60 (d, J =16.0 Hz, 1H), 6.56 (dd, J = 16.0, 7.4 Hz, 1H), 4.15 (m, 1H), 3.82 (s,3H) DC7 348 ([M + H]⁺) 8.55 (s, 1H), 8.10 (s, 3141, 1512, 1H), 7.62 (d,J = 8.8 Hz, 1246, 1118 2H), 7.5 (d, J = 8.4 Hz, 2H), 7.38 (m, 2H), 7.12(m, 2H), 6.61 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 7.6 Hz, 1H),4.15 (m, 1H) DC8 366.13 ([M + H]⁺) 8.57 (s, 1H), 8.11 (s, 3116, 1628,1H), 7.65 (d, J = 7.2 Hz, 1524, 1252, 2H), 7.52 (d, J = 8.0 Hz, 1168,1118 2H), 6.95 (m, 2H), 6.82 (m, 1H), 6.65 (d, J = 16.0 Hz, 1H), 6.50(dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H) DC9 348.11 ([M + H]⁺) 8.71 (s,1H), 8.20 (s, 3115, 1525, 1H), 7.70 (d, J = 8.0 Hz, 1248, 1174 2H), 7.57(d, J = 8.0 Hz, 2H), 7.40 (m, 1H), 7.19 (m, 3H), 6.60 (d, J = 16.0 Hz,1H), 6.40 (dd, J = 16.0, 8.4 Hz, 1H), 4.15 (m, 1H) DC10 348.11 ([M +H]⁺) 8.75 (s, 1H), 8.20 (s, 3114, 1526, 1H), 7.72 (d, J = 8.4 Hz, 1259,1238, 2H), 7.6 (d, J = 8.4 Hz, 1193, 1114 2H), 7.20-7.40 (m, 4H), 6.60(d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H, ), 4.60 (m, 1H)DC11 75.5-78.5 358.14 ([M + H]⁺) 8.55 (s, 1H), 8.10 (s, 1H), 7.65 (d, J= 8.8 Hz, 2H), 7.52 (d, J = 8.4 Hz, 2H), 7.01 (s, 3H), 6.60 (d, J = 16.0Hz, 1H), 6.51 (dd, J = 16.0, 7.8 Hz, 1H), 4.15 (m, 1H), 2.34 (s, 6H)DC12 398.05 ([M + H]⁺) 8.58 (s, 1H), 8.10 (s, 3055, 2930, 1H), 7.68 (d,J = 8.4 Hz, 1523, 1250, 2H), 7.53 (m, 4H), 1165 7.2 (s, 1H) 6.62 (d, J =15.6 Hz, 1H), 6.44 (dd, J = 15.6, 8.0 Hz, 1H), 4.15 (m, 1H) DC13 396.16([M + H]⁺) 8.58 (s, 1H), 8.10 (s, 3108, 1523, 1H), 7.62 (d, J = 8.4 Hz,1249, 1166, 2H), 7.55 (m, 4H), 1127 7.25 (m, 1H), 6.64 (d, J = 16.0 Hz,1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 4.90 (m, 1H) DC14 398.05 ([M +H]⁺) 8.58 (s, 1H), 8.10 (s, 3117, 2925, 1H), 7.62 (d, J = 8.4 Hz, 1526,1246, 2H), 7.55 (m, 4H), 1172, 1117 7.25 (m, 1H), 6.67 (d, J = 16.0 Hz,1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 5.00 (m, 1H) DC15 397.95 ([M +H]⁺) 8.58 (s, 1H), 8.10 (s, 3120, 1524, 1H), 7.66 (d, J = 8.0 Hz, 1267,1176, 2H), 7.52 (m, 3H), 1112 7.40 (d, J = 8.0 Hz, 1H), 7.30 (dd, J =8.4, 2.9 Hz, 1H), 6.64 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz,1H), 4.90 (m, 1H) DC16 466 ([M + H]⁺) 8.61 (s, 1H), 8.13 (s, 1H), 7.92(s, 1H), 7.86 (s, 2H), 7.70 (d, J = 7.0 Hz, 2H), 7.54 (d, J = 7.0 Hz,2H), 6.67 (d, J = 16.0 Hz, 1H), 6.46 (dd, J = 16.0, 8.0 Hz, 1H), 4.35(m, 1H) DC17 430.06 ([M + H]⁺) 8.58 (s, 1H), 8.1 (s, 1H), 3122, 3076,7.68 (d, J = 8.4 Hz, 2H), 2929, 1523, 7.54 (d, J = 8.4 Hz, 2H), 1250,1168, 7.51 (s, 1H), 7.42 (s, 1114 1H), 6.68 (d, J = 16.0 Hz, 1H), 6.35(dd, J = 16.0, 8.0, Hz, 1H), 4.98 (m, 1H) DC18 92-95 429.91 ([M + H]⁺)8.57 (s, 1H), 8.11 (s, 1H), 7.69 (d, J = 8.8 Hz, 2H), 7.54 (d, J = 8.4Hz, 2H), 7.42 (s, 2H), 6.65 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0,8.0 Hz, 1H), 4.10 (m, 1H) DC19 97-99 430.321 ([M + H]⁺) 8.58 (s, 1H),8.12 (s, 1H), 7.68 (d, J = 8.0 Hz, 2H), 7.64 (s, 1H), 7.59 (s, 1H), 7.55(m, 3H), 6.60 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H),4.22 (m, 1H) DC20 427.0463 (427.0466) 8.58 (s, 1H), 8.15 (s, 2937, 1524,1H), 7.70 (d, J = 8.4 Hz, 1482, 1278, 2H), 7.58 (d, J = 8.4 Hz, 1249,1166, 2H), 7.36 (s, 2H), 1112 6.62 (d, J = 16.0 Hz, 1H), 6.43 (dd, J =16.0, 8.0 Hz, 1H), 4.12 (m, 1H), 3.88 (s, 3H) DC21 412.04 ([M + H]⁺)8.42 (s, 1H), 7.60 (d, J = 8.0 Hz, 3108, 1572, 2H), 7.50 (d, J = 8.0 Hz,1531, 1242, 2H), 7.40 (s, 1172, 1104 1H), 7.22 (s, 2H), 6.60 (d, J =16.0 Hz, 1H), 6.42 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H), 2.5 (s, 3H)DC22 147-149 441.01 ([M − H]⁻) 8.62 (s, 1H), 7.78 (d, J = 8.0 Hz, 2H),7.60 (d, J = 8.0 Hz, 2H), 7.40 (s, 1H), 7.30 (s, 2H), 6.67 (d, J = 16.0Hz, 1H), 6.48 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H) DC23 412.05 ([M +H]⁺) 7.95 (s, 1H), 7.35 (d, J = 8.0 Hz, 1112, 799 2H), 7.46 (d, J = 8.0Hz, 2H), 7.39 (s, 1H), 7.29 (s, 2H), 6.67 (d, J = 16.0 Hz, 1H), 6.45(dd, J = 16.0, 8.0 Hz, 1H), 4.12 (m, 1H), 2.51 (s, 3H) DC24 133-134440.03 ([M + H]⁺) 8.10 (s, 1H), 7.52 (d, J = 8.0 Hz, 2H), 7.42-7.38 (m,3H), 7.28 (s, 2H), 6.67 (d, J = 16.0 Hz, 1H), 6.45 (dd, J = 16.0, 8.0Hz, 1H), 4.16 (m, 1H), 2.79 (s, 3H) DC25 442.02 ([M − H]⁻) 7.97 (s, 1H),7.59 (d, J = 8.0 Hz, 1167, 1114, 2H), 7.53 (d, J = 8.0 Hz, 800 2H), 7.38(m, 1H), 7.29 (s, 2H), 6.65 (d, J = 16.0 Hz, 1H), 6.42 (dd, J = 16.0,8.0 Hz, 1H), 4.17 (m, 1H), 2.74 (s, 3H) DC26 464.03 ([M − H]⁻) 8.12 (s,1H), 7.49 (d, J = 8.0 Hz, 1689, 1253, 2H), 1166, 1114, 7.40-7.37 (m 3H),7.28 (s, 2H), 979, 964 6.66 (d, J = 16.0 Hz, 1H), 6.44 (dd, J = 16.0,8.0 Hz, 1H), 4.14 (m, 1H), 3.22 (m, 1H), 1.09-1.16 (m, 4H) DC27 473.94([M − H]⁻) 8.19 (s, 1H), 7.64 (d, J = 7.2 Hz, 1571, 1331, 2H), 7.55 (d,7.2 Hz, 1170, 1113, 2H), 7.39 (s, 1H), 764 7.30 (s, 2H), 6.62 (d, J =16.0 Hz, 1H), 6.42 (dd, J = 8.0, 16.0 Hz, 1H), 4.18 (m, 1H), 3.58 (s,3H) DC28 421.22 ([M + H]⁺) 8.79 (s, 1H), 8.18 (s, 3126, 2233, 1H), 7.80(m, 3H), 1516, 1250, 7.52 (m, 2H), 7.24 (m, 1H), 1165, 1109 6.63 (d, J =16.0 Hz, 1H), 6.54 (d, J = 16.0, 7.6 Hz, 1H), 4.19 (m, 1H) DC29 421.22([M + H]⁺) 8.80 (s, 1H), 8.2 (s, 1H), 3005, 1716, 7.75-7.82 (m, 3H),1363, 1223 7.41 (t, J = 2 Hz, 1H), 7.26 (m, 2H), 6.65 (d, J = 16.0 Hz,1H), 6.52 (dd, J = 16.0, 7.6 Hz, 1H), 4.16 (m, 1H) DC30 489.17 ([M +H]⁺) 8.81 (s, 1H), 8.20 (s, 2964, 2234, 1H), 7.94 (s, 1H), 1289, 1166,7.85 (m, 3H), 7.79 (m, 2H), 1136 6.70 (d, J = 16.0 Hz, 1H), 6.58 (dd, J= 16.0, 8.0 Hz, 1H), 4.35 (m, 1H) DC31 117-118 455.27 ([M + H]⁺) 8.80(s, 1H), 8.20 (s, 1H), 7.82 (m, 3H), 7.4 (s, 2H), 6.62 (d, J = 16.0 Hz,1H), 6.52 (dd, J = 16.0, 8.0 Hz, 1H), 4.18 (m, 1H) DC32 388.0705(388.0703) 8.82 (s, 1H), 8.22 (s, 3126, 2234, 1H), 7.82-7.78 (m, 3H),1520, 1280, 7.38-7.30 (m, 3H), 1164, 1112 6.62 (d, J = 16.1 Hz, 1H),6.56 (dd, J = 16.1, 6.8 Hz, 1H), 4.18 (m, 1H) DC33 455.22 ([M − H]⁻)8.80 (s, 1H), 8.20 (s, 3122, 3086, 1H), 7.82-7.80 (m, 3H), 2234, 1517,7.70-7.50 (m, 3H), 1327, 1168, 6.65 (d, J = 16.9 Hz, 1H), 1113 6.54 (dd,J = 16.9, 6.8 Hz, 1H), 4.25 (m, 1H) DC34 452.0412 (452.0419) 8.85 (s,1H), 8.23 (br s, 3122, 2934, 1H), 7.83-7.78 (m, 3H), 2231, 1516, 7.33(s, 2H), 6.69 (d, J = 14.9 Hz, 1480, 1248, 1H), 6.50 (dd, 1211, 1165, J= 14.9, 7.2 Hz, 1H), 1111 4.15 (m, 1H), 3.90 (s, 3H) DC35 439.01 ([M −H]⁻) 8.60 (s, 1H), 8.20 (s, 2233, 1518, 1H), 7.82 (m, 3H), 1250, 1169,7.28 (m, 2H), 6.65 (d, J = 16.0 Hz, 1035, 817 1H), 6.48 (dd, J = 16.0,8.0 Hz, 1H), 4.20 (m, 1H) DC36 437.25 ([M + H]⁺) 8.70 (s, 1H), 7.80 (m,2927, 2233, 3H), 7.40 (s, 1H), 1572, 1531, 7.28 (s, 2H), 6.63 (d, J =16.0 Hz, 1248, 1166, 1H), 6.50 (dd, J = 16.0, 1112 8.0 Hz, 1H), 4.18 (m,1H), 2.50 (s, 1H) DC37 109-111 466.10 ([M − H]⁻) 8.86 (s, 1H), 7.89 (m,3H), 7.40 (s, 1H), 7.30 (s, 2H), 6.68 (d, J = 16.0 Hz, 1H), 6.57 (dd, J= 16.0, 8.0 Hz, 1H), 4.18 (m, 1H) DC38 96-98 436.11 ([M − H]⁻) 8.58 (s,1H), 7.75 (m, 3H), 7.40 (s, 1H), 7.28 (s, 2H), 6.61 (d, J = 16.0 Hz,1H), 6.42 (dd, J = 16.0, 8.2 Hz, 1H), 4.40 (br s, 2H), 4.15 (m, 1H) DC39224-226 480.30 ([M + H]⁺) 8.65 (s, 1H), 8.18 (br s, 3352, 2237, 1H),7.80-7.70 (m, 3H), 1707, 1163, 7.40 (s, 1H), 7.27 (s, 841 2H), 7.36 (m,1H), 7.28 (m, 2H), 6.60 (d, J = 16.8 Hz, 1H), 6.47 (m, 1H), 4.16 (m,1H), 2.40 (br s, 3H) DC40 70-73 436.11 ([M − 2H]⁻) 8.86 (s, 1H), 7.88(m, 3H), 7.44 (s, 2H), 6.67 (d, J = 16.0 Hz, 1H), 6.56 (dd, J = 16.0 7.6Hz, 1H), 4.19 (m, 1H) DC41 72-75 469.95 ([M − H]⁻) (DMSO-d₆) 8.72 (s,1H), 8.26 (s, 1H), 8.01 (d, J = 8.4 Hz, 1H), 7.91 (s, 2H), 7.77 (d, J =8.4 Hz, 1H), 6.42 (dd, J = 15.6, 9.2 Hz, 1H), 6.83 (d, J = 15.6 Hz, 1H),5.87 (s, 2H), 4.89 (m, 1H) DC42 104-107 609.98 ([M + H]⁺) 8.78 (s, 2H),7.83 (s, 2234, 1714, 1H), 7.80 (m, 2H), 1114, 807 7.42 (s, 2H), 6.65 (d,J = 16.4 Hz, 1H), 6.51 (dd, J = 16.4, 7.8 Hz, 1H), 4.17 (m, 1H), 42.16(m, 2H), 1.25 (m, 4H), 1.00 (m, 4H), DC43 109-112 540.04 ([M + H]⁺)(DMSO-d₆) 10.94 (br s, 3233, 2233, 1H), 8.36 (s, 1H), 1699, 1114, 8.08(m, J = 8.4 Hz, 1H), 807 7.91 (s, 2H), 7.84 (d, J = 8.4 Hz, 1H), 7.13(dd, J = 15.6, 9.2 Hz, 1H), 6.87 (d, J = 15.6 Hz, 1H), 4.92 (m, 1H),1.99 (br s, 1H), 0.82 (s, 4H) DC44 435.26 [M − H]⁻ 8.33 (s, 1H), 8.23(s, 2236, 1510, 1H), 7.66 (s, 1H), 1114, 801 7.60 (s, 1H), 7.41 (m, 1H),7.28 (m, 2H), 6.62 (d, J = 16.0 Hz, 1H), 6.51 (dd, J = 16.0, 7.8 Hz,1H), 4.16 (m, 1H), 2.20 (s, 3H) DC45 75-78 468.87 [M − H]⁻ 8.36 (s, 1H),8.23 (s, 1H), 7.66 (s, 1H), 7.60 (s, 1H), 7.41 (s, 2H), 6.62 (d, J =16.4 Hz, 1H), 6.51 (dd, J = 16.4, 7.6 Hz, 1H), 4.16 (m, 1H), 2.20 (s,3H) DC46 411.4 ([M]⁺) 8.83 (s, 1H), 8.21 (s, ¹³C NMR (δ)³ 1H), 7.83 (d,J = 8.5 Hz, 155.63, 1H), 7.61 (d, J = 1.9 Hz, 153.27, 1H), 7.52 (dd, J =8.4, 153.12, 1.9 Hz, 1H), 7.28 (d, J = 3.8 Hz, 143.01, 2H), 6.93 (d, J =11.5 Hz, 137.89, 1H), 136.25, 6.26-6.20 (m, 1H), 4.22 (m, 134.03, 1H)133.88, 132.23, 131.23, 131.18, 129.20, 126.17, 125.04, 124.99 DC47139-141 474.16 ([M − H]⁻) 8.51 (s, 1H), 8.14 (s, 1H), 7.75 (s, 1H), 7.5(m, 2H), 7.4 (s, 1H), 7.30 (m, 2H), 6.60 (d, J = 16.0 Hz, 1H), 6.50 (dd,J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H) DC48 124-126 414.05 [M − H]⁻ 8.69(s, 1H), 8.14 (s, 1H), 7.96 (d, J = 4.8 Hz, 1H), 7.39-7.27 (m, 5H), 6.95(d, J = 16.0 Hz, 1H), 6.51 (dd, J = 16.0, 7.6 Hz, 1H), 4.13 (m, 1H) DC4981-83 463.96 [M − H]⁻ 8.57 (s, 1H), 8.14 (s, 1H), 7.60 (m, 2H), 7.44 (m,3H), 6.95 (d, J = 16.0 Hz, 1H), 6.51 (dd, J = 16.0, 7.6 Hz, 1H), 4.13(m, 1H) DC50 140-143 430.07 [M − H]⁻) 8.56 (s, 1H), 8.13 (s, 1110, 8031H), 7.59 (d, J = 1.2 Hz, 2H), 7.44 (m, 2H), 7.28 (m, 2H), 6.61 (d, J =16.0 Hz, 1H), 6.47 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H) DC51 118-121464.22 ([M − H]⁻) 8.32 (s, 1H), 8.15 (s, 1H), 7.82 (s, 1H), 7.73 (d, J =8.4 Hz, 1H), 7.53 (d, J = 8.4 Hz, 1H), 7.41 (s, 1H), 7.29 (s, 2H), 6.70(d, J = 15.6 Hz, 1H), 6.50 (dd, J = 15.6, 8.0 Hz, 1H), 4.20 (m, 1H) DC529.99 (s, 1H), 8.42 (s, 3123, 3079, 1H), 8.12 (s, 1H), 2925, 1692, 8.01(s, 1H), 7.68 (m, 1H), 1571, 1512, 7.44 (m, 1H), 7.33 (m, 1253, 1164,1H), 7.22 (s, 2H), 1111 6.62 (d, J = 16.7 Hz, 1H), 6.45 (dd, J = 16.7,9.3 Hz, 1H), 4.10 (m, 1H) DC53 8.30 (m, 1H), 8.00 (br s, 3250, 3043,1H), 7.75 (m, 1H), 1683, 1116 7.68 (m, 1H), 7.55 (m, 1H), 7.36 (m, 1H),7.28 (m, 2H), 6.70 (m, 1H), 6.58 (br s, 1H), 6.33 (m, 1H), 5.88 (m, 2H),4.10 (m, 1H) DC54 56-58 441.07 ([M − H]⁻) 8.40 (s, 1H), 8.13 (s, 1H),8.02 (s, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.4(s, 1H), 7.29 (m, 2H), 6.69 (d, J = 15.6 Hz, 1H), 6.57 (dd, J = 15.6,7.8 Hz, 1H), 4.15 (m, 1H) DC55 412.97 ([M + H]⁺) 8.37 (s, 1H), 8.18 (s,1H), 7.39 (s, 1H), 7.30 (m, 2H), 7.19 (d, J = 8.0 Hz, 1H), 6.90 (m, 2H),6.55 (d, J = 15.6 Hz, 1H), 6.38 (dd, J = 15.6, 8.2 Hz, 1H), 4.20 (m,1H), 2.50 (br s, 2H) DC56 175-177 453 ([M − H]⁻) 9.59 (br s, 1H), 8.55(s, 1H), 8.47 (s, 2H), 8.23 (s, 1H), 7.30 (m, 4H), 6.62 (d, J = 16.0 Hz,1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H), 2.20 (s, 3H) DC57426.0627 (426.0626) 8.33 (s, 1H), 8.16 (s, 3342, 3112, 1H), 7.38 (s,1H), 2931, 1606, 7.29 (s, 2H), 7.15 (d, J = 7.6 Hz, 1583, 1574, 1H),6.80 (d, J = 7.6 Hz, 1528, 1153 1H), 6.74 (m, 1H), 6.60 (d, J = 15.6 Hz,1H), 6.35 (dd, J = 15.6, 8.4 Hz, 1H), 5.40 (br s, 1H), 4.15 (m, 1H),2.90 (s, 3H) DC58 94-97 440.0424 (440.0419) (DMSO-d₆) 8.76 (s, 3403,3304, 1H), 8.16 (s, 1H), 3178, 1674, 7.90 (br s, 1H), 7.83 (s, 1H),1571, 1169, 7.70 (d, J = 7.9 Hz, 1H), 1108 7.71-7.67 (m, 3H), 7.58 (d, J= 7.9 Hz, 1H), 7.52 (br s, 1H), 7.00 (dd, J = 15.8, 8.7 Hz, 1H), 6.85(d, J = 15.8 Hz, 1H), 4.85 (m, 1H) DC59 87-90 (DMSO-d₆) 9.00 (s, 1H),8.63 (s, 1H), 8.17 (s, 1H), 7.70-7.59 (m, 5H), 7.00 (dd, J = 16.2, 9.7Hz, 1H), 6.85 (d, J = 16.2 Hz, 1H), 5.90 (br s 2H), 4.83 (m, 1H) DC60469.0577 (469.0572) 8.32 (s, 1H), 8.10 (s, 2987, 1725, 1H), 7.97 (s,1H), 1518, 1275, 7.65 (d, J = 8.1 Hz, 1H), 1166, 1113 7.47 (d, J = 8.1Hz, 1H), 7.40 (m, 1H), 7.28 (s, 2H), 6.62 (d, J = 16.5 Hz, 1H), 6.49(dd, J = 16.5, 7.7 Hz, 1H), 4.23-4.04 (m, 3H), 1.15 (t, J = 8.0 Hz, 3H)DC61 130-132 442.15 ([M + H]⁺) (DMSO-d₆) 9.90 (s, 1H), 8.17 (s, 1H),8.15 (m, 1H), 7.90 (m, 1H), 7.71 (m, 2H), 7.67 (m, 1H), 7.62 (d, J = 7.3Hz, 1H), 7.03 (dd, J = 16.5, 8.3 Hz, 1H), 6.62 (d, J = 16.5 Hz, 1H),4.87 (m, 1H) DC62 412.10 ([M + H]⁺) 8.27 (s, 1H), 8.23 (s, 1513, 1252,1H), 7.40 (m, 3H), 1166, 1112, 7.30 (m, 3H), 6.64 (d, J = 16.0 Hz, 8011H), 6.45 (dd, J = 16.0, 8.0 Hz, 1H), 4.19 (m, 1H), 2.21 (s, 3H) DC63446.01 ([M + H]⁺) 8.26 (s, 1H), 8.12 (s, 2928, 1H), 7.42 (s, 2H), 2525,1249, 7.18-7.28 (m, 3H), 6.62 (d, J = 15.6 Hz, 1169, 1114, 1H), 809 6.39(dd, J = 15.6, 9.4 Hz, 1H), 4.10 (m, 1H), 2.25 (s, 3H) DC64 475.03 ([M +H]⁺) 8.84 (d, J = 5.8 Hz, 2H), 1683, 1167, 8.33 (s, 1H), 8.20 (s, 650,479 1H), 7.75 (m, 1H), 7.60 (d, J = 28.6 Hz, 1H), 7.58-7.48 (m, 3H),7.42 (m, 1H), 7.28 (s, 2H), 6.71 (d, J = 16.9 Hz, 1H), 6.39 (dd, J =16.9, 8.2 Hz, 1H), 4.15 (m, 1H) DC65 412.05 ([M + H]⁺) 8.55 (s, 1H),8.12 (s, 722, 111 1H), 7.55 (m, 3H), 7.39 (m, 1H), 7.30 (d, J = 1.6 Hz,1H), 6.85 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0, 8.0 Hz, 1H), 4.17(m, 1H), 2.40 (s, 3H) DC66 60-61 468.26 ([M + H]⁺) 8.59 (s, 1H), 8.14(s, 1H), 7.94 (s, 1H), 7.70 (d, J = 8.0 Hz, 1H), 7.61 (d, J = 8.0 Hz,1H), 7.43 (s, 2H), 7.23 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0, 8.0Hz, 1H), 4.20 (m, 1H) DC67 133-134 432.30 ([M + H]⁺) 8.59 (s, 1H), 8.12(s, 800, 114 1H), 7.78 (br s, 1H), 7.71 (m, 1H), 7.62 (m, 1H), 7.39 (s,1H), 7.32 (s, 2H), 7.03 (d, J = 16.0 Hz, 1H), 6.43 (dd, J = 16.0, 8.0Hz, 1H), 0.21 (m, 1H) DC68 412.03 ([M + H]⁺) 8.71 (s, 1H), 8.18 (s, 1H),7.71 (d, J = 8.0 Hz, 2H), 7.55 (d, J = 8.0 Hz, 2H), 7.37 (s, 1H), 7.28(m, 2H), 6.08 (d, J = 16.0 Hz, 1H), 4.26 (m, 1H), 2.05 (s, 3H) DC69162-168 414.03 ([M + H]⁺) 8.56 (s, 1H), 8.11 (s, 1H), 7.70 (d, J = 8.5Hz, 2H), 7.56 (d, J = 8.5 Hz, 2H), 7.54 (m, 2H), 7.40 (m, 1H), 6.91 (d,J = 16.5 Hz, 1H), 6.66 (d, J = 16.5 Hz, 1H) DC70  99-103 428.05 ([M +H]⁺) 8.58 (s, 1H), 8.13 (s, 1H), 7.73 (d, J = 8.7 Hz, 2H), 7.60 (d, J =8.7 Hz, 2H), 7.46 (m, 2H), 7.42 (m, 1H), 6.85 (d, J = 16.2 Hz, 1H), 6.40(d, J = 16.2 Hz, 1H), 3.42 (s, 3H) ^(a) ¹H NMR spectral data wereacquired using a 400 MHz instrument in CDCl₃ except where noted. HRMSdata are noted observed value (theoretical value).

TABLE 2A Analytical Data for Compounds in Table 1A. Compound mp IR(cm⁻¹); Number (° C.) ESIMS ¹H NMR (δ)^(a) ¹⁹F NMR F1 588.10 ([M + H]⁺)(400 MHz, CDCl₃) δ ¹⁹F NMR 7.64 (d, J = 1.6 Hz, (376 MHz, 1H), 7.61 (s,1H), CDCl₃) δ −68.56 7.58 (d, J = 8.0 Hz, 1H), 7.43 (dd, J = 8.1, 1.6Hz, 1H), 7.41 (s, 2H), 6.55 (d, J = 15.9 Hz, 1H), 6.42 (dd, J = 16.0,7.7 Hz, 1H), 5.33 (s, 1H), 4.12 (m, 1H), 3.29 (m, 5H), 1.15 (t, J = 7.2Hz, 3H). F7 627.9 ([M + H]⁺) 8.12 (s, 1H), 7.65 (s, ¹⁹F NMR 1H), 7.60(d, J = 8.0 Hz, (376 MHz, 1H), 7.50 (s, 1H), CDCl₃) δ −68.56, 7.40 (s,3H), 6.54 (d, J = 15.8 Hz, −73.02 1H), 6.42 (dd, J = 16.0, 7.7 Hz, 1H),5.95 (t, 1H), 4.10 (q, J = 8.9 Hz, 1H), 3.91 (m, 2H). ^(a1)H NMRspectral data were acquired using a 400 MHz instrument in CDCl₃ exceptwhere noted. HRMS data are noted observed value (theoretical value).

TABLE 2B Analytical Data for Compounds in Table 1B. Compound mp IR(cm⁻¹); Number (° C.) ESIMS ¹H NMR (δ)^(a) ¹⁹F NMR FA1 637.9 ([M − H]⁻)(300 MHz, DMSO-d₆) δ 3444, 1649, 10.45 (s, 1H), 7.98 (s, 1261, 749 1H),7.91 (s, 2H), 7.74 (d, J = 7.5 Hz, 1H), 7.66 (d, J = 7.5 Hz, 1H), 7.19(t, J = 6.3 Hz, 1H), 7.04 (dd, J = 15.9, 9.3 Hz, 1H), 6.79 (d, J = 15.6Hz, 1H), 4.88-4.81 (m, 1H), 3.86-3.78 (m, 2H), 3.08 (s, 3H) FA2 628.0([M − H]⁻) (300 MHz, DMSO-d₆) δ 3395, 1698, 10.53 (s, 1H), 8.06 (s,1163, 809 1H), 7.96 (s, 2H), 7.92 (s, 2H), 7.23 (bs, 1H), 7.14 (dd, J =15.3, 9.0 Hz, 1H), 6.91 (d, J = 15.9 Hz, 1H), 4.89-4.82 (m, 1H),3.86-3.81 (m, 2H), 3.02 (s, 3H) FA3 575.7 ([M − CH₂CF₃]⁺) (300 MHz,DMSO-d₆) δ ¹⁹F NMR 9.87 (s, 1H), 8.00 (s, (300 MHz, 1H), 7.92-7.87 (m,DMSO-d₆) δ −57.86, 3H), 7.49 (d, J = 7.8 Hz, −67.95, 1H), 7.10 (dd, J =15.3, −71.72 8.7 Hz, 1H), 6.89 (d, J = 15.6 Hz, 1H), 6.80 (t, J = 6.3Hz, 1H), 4.89-4.82 (m, 1H), 3.90-3.78 (m, 2H), 3.11-3.07 (m, 1H), 1.01(d, J = 6.3 Hz, 6H). FA4 684.4 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3395,1698, 10.52 (s, 1H), 8.06 (s, 1163, 809 1H), 7.96 (s, 2H), 7.90 (s, 1H),7.85 (s, 2H), 7.24 (t, J = 6.0 Hz, 1H), 7.14 (dd, J = 15.6, 9.0 Hz, 1H),6.90 (d, J = 15.9 Hz, 1H), 4.88-4.80 (m, 1H), 3.86-3.78 (m, 2H), 3.02(s, 3H) FA5 715.6 ([M − H]⁻) (400 MHz, DMSO-d₆) δ 10.53 (s, 1H), 8.05(s, 3H), 7.96 (s, 2H), 7.24 (t, J = 6.4 Hz, 1H), 7.13 (dd, J = 15.6, 9.2Hz, 1H), 6.89 (d, J = 15.6 Hz, 1H), 4.88-4.83 (m, 1H), 3.86-3.82 (m,2H), 3.02 (s, 3H) FA6 674.0 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3390, 2925,10.53 (s, 1H), 8.06 (s, 1673, 1165, 1H), 7.96 (s, 2H), 750 7.88 (s, 1H),7.69 (s, 1H), 7.23 (t, J = 6.0 Hz, 1H), 7.13 (dd, J = 15.6, 8.7 Hz, 1H),6.91 (d, J = 15.6 Hz, 1H), 4.89-4.83 (m, 1H), 3.86-3.81 (m, 2H), 3.02(s, 3H) FA7 611.8 ([M − H]⁻) (400 MHz, DMSO-d₆) δ 10.53 (s, 1H), 8.06(s, 1H), 7.96 (s, 2H), 7.88 (d, J = 6.4 Hz, 2H), 7.24 (t, J = 6.4 Hz,1H), 7.12 (dd, J = 15.6, 8.8 Hz, 1H), 6.89 (d, J = 16.0 Hz, 1H),4.87-4.82 (m, 1H), 3.86-3.77 (m, 2H), 3.02 (s, 3H) FA8 115-119 614.4([M + H]⁺) (300 MHz, DMSO-d₆) δ 10.50 (bs, 1H), 8.07-8.05 (m, 1H),7.95-7.92 (m, 4H), 7.14 (dd, J = 16.2, 9.0 Hz, 1H), 6.91 (d, J = 15.9Hz, 1H), 6.15-5.78 (m, 1H), 4.90-4.84 (m, 1H), 3.49-3.39 (m, 2H), 3.01(s, 3H) FA9 112-115 645.6 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 10.44 (bs,1H), 8.06-8.05 (m, 1H), 7.93-7.92 (m, 4H), 7.08 (dd, J = 15.6, 9.0 Hz,1H), 6.91 (d, J = 15.3 Hz, 1H), 6.79 (bs, 1H), 4.88-4.85 (m, 1H),3.37-3.24 (m, 2H), 2.99 (s, 3H), 2.43-2.38 (m, 2H) FA10 644.7 ([M + H]⁺)8.00 (t, J = 6.5 Hz, 1H), ¹⁹F NMR 7.73-7.62 (m, 2H), (376 MHz, 7.44-7.34(m, 3H), CDCl₃) δ −59.79, 6.65 (d, J = 15.9 Hz, −68.59, 1H), 6.47 (dd, J= 15.9, −72.70. 7.8 Hz, 1H), 4.19-4.11 (m, 1H), 4.11-3.98 (m, 4H), 3.89(m, 2H) ^(a1)H NMR spectral data were acquired using a 400 MHzinstrument in CDCl₃ except where noted. HRMS data are noted observedvalue (theoretical value).

TABLE 3 Assays Results Compound BAW CEW GPA Number Rating Rating RatingAC1 D D B AC2 C C C AC3 D D B AC4 D A B AC5 D D B AC6 D A B AC7 A A BAC8 D B B AC9 A A B AC10 A A B AC11 A A D AC12 A A D AC13 A A B AC14 A BD AC15 A A B AC16 A A C AC17 A A B AC18 A A B AC19 D D B AC20 A A C AC21D D C AC22 A A D AC23 A A B AC24 A A D AC25 A A D AC26 A A B AC27 A A BAC28 A A B AC29 A A B AC30 A A B AC31 A A B AC32 A A B AC33 A A B AC34 AA B AC35 A A C AC36 A A B AC37 A A B AC38 A A C AC39 A A C AC40 A A DAC41 A D D AC42 A D D AC43 A A B AC44 A A B AC45 A A D AC46 A A D AC47 DD B AC48 A A B AC49 A A B AC50 A D B AC51 A A B AC52 A A B AC53 A A BAC54 A A B AC57 A A B AC58 A A B AC59 A A B AC60 A A B AC61 A A B AC62 AA D AC63 A A B AC64 A A B AC65 A A B AC66 A A B AC67 A A B AC68 A A DAC69 A A A AC70 D D B AC71 A A B AC72 A A B AC75 A A B AC76 A A D AC77 AA B AC78 A A A AC79 A A A AC80 A A B AC81 A D D AC82 A A B AC83 A A BAC84 A A D AC85 A A B AC86 A A D AC87 A A B AC89 A A B AC90 A A C AC91 AA C AC92 A A C AC93 A D C AC94 D B B AC95 A A C AC96 D D C AC97 D D CAC98 A A C AC99 A A C AC100 C C C AC101 D D C AC102 D A C AC103 A A DAC104 A A B AC105 A A D AC106 A A B AC107 B A D AC108 B D D AC109 D D CAC110 A A C AC111 A A C AC112 A A C AC113 B A D AC114 A B D AC115 A A DAC116 C C C AC117 A D B AC118 A D D BC1 A A D BC2 A A D BC3 A A D BC4 AA B BC5 A A B BC6 A A D BC7 A A D BC8 A A B BC9 A A D BC10 A A B BC11 CC C BC12 C C C BC13 A A D BC14 A D D CC1 D D D CC2 A A B CC3 A A D CC4 AB B CC5 A A B CC6 A A B CC7 A A B CC8 A A D CC9 A A B CC10 A A B CC11 AA B CC12 D D B CC13 A A B CC14 A D D CC15 A A B CC16 A A B CC17 A A BCC18 A A B CC19 A A B CC20 A A D CC21 A A D CC22 A A B CC23 A A B CC24 AA D CC25 A A B CC26 A D B CC27 A A D CC28 A A D CC29 A A B CC30 A A DCC31 B D C CC32 A A B CC33 A A B CC34 A A B CC35 D D D CC36 A A D CC37 AA D CC38 A A D CC39 D D B CC40 D A D CC41 D D B CC42 D D D CC43 A B BCC44 A A B CC45 A A D CC46 D A C CC47 D D C CC48 D D C CC49 D D D CC50 AA D CC51 A A D CC52 A D D CC53 D D B CC54 A A C DC1 A A D DC2 D D C DC3B D C DC4 A D C DC5 D D C DC6 D D C DC7 A D C DC8 A D C DC9 D D C DC10 DD C DC11 A D C DC12 A A B DC13 A A C DC14 D D C DC15 D D C DC16 A A CDC17 A A C DC18 A A C DC19 A A C DC20 A D C DC21 D D C DC22 D D C DC23 DA C DC24 D D C DC25 D D C DC26 D D C DC27 D D C DC28 A A B DC29 A A CDC30 A A C DC31 A A B DC32 D D C DC33 A A C DC34 A A B DC35 A A B DC36 DD C DC37 A A C DC38 A A C DC39 A A C DC40 A A C DC41 A A C DC42 A A CDC43 A A C DC44 A A C DC45 A A C DC46 A A C DC47 A A C DC48 A A C DC49 AA C DC50 A A C DC51 A A C DC52 D D C DC53 D A C DC54 D D C DC55 D D CDC56 D D C DC57 A A C DC58 D D C DC59 D D C DC60 A A C DC61 D D C DC62 AA C DC63 A A C DC64 D D C DC65 D A C DC66 A A C DC67 A A C DC68 A A CDC69 D D C DC70 A A C

TABLE 3A Assays Results Compound BAW CL GPA Number Rating Rating RatingF1 A A C F7 A A C

TABLE 3B Assays Results Compound BAW CL GPA Number Rating Rating RatingFA1 A A C FA2 A A C FA3 C C C FA4 A A C FA5 A A C FA6 A A C FA7 A A CFA8 A A C FA9 A A C FA10 D D C

We claim:
 1. A composition comprising a molecule according to FormulaOne:

wherein: (a) R1 is H; (b) R2 is F, Cl, Br, or I; (c) R3 is F, Cl, Br, orI; (d) R4 is F, Cl, Br, or I; (e) R5 is H; (f) R6 is a (C₁-C₈)haloalkyl;(g) R7 is H; (h) R8 is H; (i) R9 is H; (j) R10 is F, Cl, Br, I, orhalo(C₁-C₈)alkyl; (k) R11 isC(═X5)N(H)((C₀-C₈)alkyl)N(R11a)(C(═X5)N(H)(R11b)) wherein X5 is 0,wherein R11a is H or (C₁-C₈)alkyl, and wherein each R11b ishalo(C₁-C₈)alkyl; (l) R12 is H; (m) R13 is H; (r) X1 is CR12; (s) X2 isCR13; and (t) X3 is CR9.
 2. A composition according to claim 1 furthercomprising: (a) one or more compounds having acaricidal, algicidal,avicidal, bactericidal, fungicidal, herbicidal, insecticidal,molluscicidal, nematicidal, rodenticidal, or virucidal properties; or(b) one or more compounds that are antifeedants, bird repellents,chemosterilants, herbicide safeners, insect attractants, insectrepellents, mammal repellents, mating disrupters, plant activators,plant growth regulators, or synergists; or (c) both (a) and (b).
 3. Acomposition according to claim 1 wherein further comprising one or morecompounds selected from: (3-ethoxypropyl)mercury bromide,1,2-dichloropropane, 1,3-dichloropropene, 1-methylcyclopropene,1-naphthol, 2-(octylthio)ethanol, 2,3,5-tri-iodobenzoic acid, 2,3,6-TBA,2,3,6-TBA-dimethylammonium, 2,3,6-TBA-lithium, 2,3,6-TBA-potassium,2,3,6-TBA-sodium, 2,4,5-T, 2,4,5-T-2-butoxypropyl, 2,4,5-T-2-ethylhexyl,2,4,5-T-3-butoxypropyl, 2,4,5-TB, 2,4,5-T-butomethyl, 2,4,5-T-butotyl,2,4,5-T-butyl, 2,4,5-T-isobutyl, 2,4,5-T-isoctyl, 2,4,5-T-isopropyl,2,4,5-T-methyl, 2,4,5-T-pentyl, 2,4,5-T-sodium,2,4,5-T-triethylammonium, 2,4,5-T-trolamine, 2,4-D,2,4-D-2-butoxypropyl, 2,4-D-2-ethylhexyl, 2,4-D-3-butoxypropyl,2,4-D-ammonium, 2,4-DB, 2,4-DB-butyl, 2,4-DB-dimethylammonium,2,4-DB-isoctyl, 2,4-DB-potassium, 2,4-DB-sodium, 2,4-D-butotyl,2,4-D-butyl, 2,4-D-diethylammonium, 2,4-D-dimethylammonium,2,4-D-diolamine, 2,4-D-dodecylammonium, 2,4-DEB, 2,4-DEP, 2,4-D-ethyl,2,4-D-heptylammonium, 2,4-D-isobutyl, 2,4-D-isoctyl, 2,4-D-isopropyl,2,4-D-isopropylammonium, 2,4-D-lithium, 2,4-D-meptyl, 2,4-D-methyl,2,4-D-octyl, 2,4-D-pentyl, 2,4-D-potassium, 2,4-D-propyl, 2,4-D-sodium,2,4-D-tefuryl, 2,4-D-tetradecylammonium, 2,4-D-triethylammonium,2,4-D-tris(2-hydroxypropyl)ammonium, 2,4-D-trolamine, 2iP,2-methoxyethylmercury chloride, 2-phenylphenol, 3,4-DA, 3,4-DB, 3,4-DP,4-aminopyridine, 4-CPA, 4-CPA-potassium, 4-CPA-sodium, 4-CPB, 4-CPP,4-hydroxyphenethyl alcohol, 8-hydroxyquinoline sulfate,8-phenylmercurioxyquinoline, abamectin, abscisic acid, ACC, acephate,acequinocyl, acetamiprid, acethion, acetochlor, acetophos, acetoprole,acibenzolar, acibenzolar-S-methyl, acifluorfen, acifluorfen-methyl,acifluorfen-sodium, aclonifen, acrep, acrinathrin, acrolein,acrylonitrile, acypetacs, acypetacs-copper, acypetacs-zinc, alachlor,alanycarb, albendazole, aldicarb, aldimorph, aldoxycarb, aldrin,allethrin, allicin, allidochlor, allosamidin, alloxydim,alloxydim-sodium, allyl alcohol, allyxycarb, alorac, alpha-cypermethrin,alpha-endosulfan, ametoctradin, ametridione, ametryn, amibuzin,amicarbazone, amicarthiazol, amidithion, amidoflumet, amidosulfuron,aminocarb, aminocyclopyrachlor, aminocyclopyrachlor-methyl,aminocyclopyrachlor-potassium, aminopyralid, aminopyralid-potassium,aminopyralid-tris(2-hydroxypropyl)ammonium, amiprofos-methyl,amiprophos, amisulbrom, amiton, amiton oxalate, amitraz, amitrole,ammonium sulfamate, ammonium α-naphthaleneacetate, amobam, ampropylfos,anabasine, ancymidol, anilazine, anilofos, anisuron, anthraquinone,antu, apholate, aramite, arsenous oxide, asomate, aspirin, asulam,asulam-potassium, asulam-sodium, athidathion, atraton, atrazine,aureofungin, aviglycine, aviglycine hydrochloride, azaconazole,azadirachtin, azafenidin, azamethiphos, azimsulfuron, azinphos-ethyl,azinphos-methyl, aziprotryne, azithiram, azobenzene, azocyclotin,azothoate, azoxystrobin, bachmedesh, barban, barium hexafluorosilicate,barium polysulfide, barthrin, BCPC, beflubutamid, benalaxyl,benalaxyl-M, benazolin, benazolin-dimethylammonium, benazolin-ethyl,benazolin-potassium, bencarbazone, benclothiaz, bendiocarb, benfluralin,benfuracarb, benfuresate, benodanil, benomyl, benoxacor, benoxafos,benquinox, bensulfuron, bensulfuron-methyl, bensulide, bensultap,bentaluron, bentazone, bentazone-sodium, benthiavalicarb,benthiavalicarb-isopropyl, benthiazole, bentranil, benzadox,benzadox-ammonium, benzalkonium chloride, benzamacril,benzamacril-isobutyl, benzamorf, benzfendizone, benzipram,benzobicyclon, benzofenap, benzofluor, benzohydroxamic acid,benzoximate, benzoylprop, benzoylprop-ethyl, benzthiazuron, benzylbenzoate, benzyladenine, berberine, berberine chloride, beta-cyfluthrin,beta-cypermethrin, bethoxazin, bicyclopyrone, bifenazate, bifenox,bifenthrin, bifujunzhi, bilanafos, bilanafos-sodium, binapacryl,bingqingxiao, bioallethrin, bioethanomethrin, biopermethrin,bioresmethrin, biphenyl, bisazir, bismerthiazol, bispyribac,bispyribac-sodium, bistrifluoron, bitertanol, bithionol, bixafen,blasticidin-S, borax, Bordeaux mixture, boric acid, boscalid,brassinolide, brassinolide-ethyl, brevicomin, brodifacoum,brofenvalerate, brofluthrinate, bromacil, bromacil-lithium,bromacil-sodium, bromadiolone, bromethalin, bromethrin, bromfenvinfos,bromoacetamide, bromobonil, bromobutide, bromocyclen, bromo-DDT,bromofenoxim, bromophos, bromophos-ethyl, bromopropylate, bromothalonil,bromoxynil, bromoxynil butyrate, bromoxynil heptanoate, bromoxyniloctanoate, bromoxynil-potassium, brompyrazon, bromuconazole, bronopol,bucarpolate, bufencarb, buminafos, bupirimate, buprofezin, Burgundymixture, busulfan, butacarb, butachlor, butafenacil, butamifos,butathiofos, butenachlor, butethrin, buthidazole, buthiobate, buthiuron,butocarboxim, butonate, butopyronoxyl, butoxycarboxim, butralin,butroxydim, buturon, butylamine, butylate, cacodylic acid, cadusafos,cafenstrole, calcium arsenate, calcium chlorate, calcium cyanamide,calcium polysulfide, calvinphos, cambendichlor, camphechlor, camphor,captafol, captan, carbamorph, carbanolate, carbaryl, carbasulam,carbendazim, carbendazim benzenesulfonate, carbendazim sulfite,carbetamide, carbofuran, carbon disulfide, carbon tetrachloride,carbophenothion, carbosulfan, carboxazole, carboxide, carboxin,carfentrazone, carfentrazone-ethyl, carpropamid, cartap, cartaphydrochloride, carvacrol, carvone, CDEA, cellocidin, CEPC, ceralure,Cheshunt mixture, chinomethionat, chitosan, chlobenthiazone,chlomethoxyfen, chloralose, chloramben, chloramben-ammonium,chloramben-diolamine, chloramben-methyl, chloramben-methylammonium,chloramben-sodium, chloramine phosphorus, chloramphenicol,chloraniformethan, chloranil, chloranocryl, chlorantraniliprole,chlorazifop, chlorazifop-propargyl, chlorazine, chlorbenside,chlorbenzuron, chlorbicyclen, chlorbromuron, chlorbufam, chlordane,chlordecone, chlordimeform, chlordimeform hydrochloride,chlorempenthrin, chlorethoxyfos, chloreturon, chlorfenac,chlorfenac-ammonium, chlorfenac-sodium, chlorfenapyr, chlorfenazole,chlorfenethol, chlorfenprop, chlorfenson, chlorfensulphide,chlorfenvinphos, chlorfluazuron, chlorflurazole, chlorfluren,chlorfluren-methyl, chlorflurenol, chlorflurenol-methyl, chloridazon,chlorimuron, chlorimuron-ethyl, chlormephos, chlormequat, chlormequatchloride, chlomidine, chlornitrofen, chlorobenzilate,chlorodinitronaphthalenes, chloroform, chloromebuform, chloromethiuron,chloroneb, chlorophacinone, chlorophacinone-sodium, chloropicrin,chloropon, chloropropylate, chlorothalonil, chlorotoluron, chloroxuron,chloroxynil, chlorphonium, chlorphonium chloride, chlorphoxim,chlorprazophos, chlorprocarb, chlorpropham, chlorpyrifos,chlorpyrifos-methyl, chlorquinox, chlorsulfuron, chlorthal,chlorthal-dimethyl, chlorthal-monomethyl, chlorthiamid, chlorthiophos,chlozolinate, choline chloride, chromafenozide, cinerin I, cinerin II,cinerins, cinidon-ethyl, cinmethylin, cinosulfuron, ciobutide,cisanilide, cismethrin, clethodim, climbazole, cliodinate, clodinafop,clodinafop-propargyl, cloethocarb, clofencet, clofencet-potassium,clofentezine, clofibric acid, clofop, clofop-isobutyl, clomazone,clomeprop, cloprop, cloproxydim, clopyralid, clopyralid-methyl,clopyralid-olamine, clopyralid-potassium,clopyralid-tris(2-hydroxypropyl)ammonium, cloquintocet,cloquintocet-mexyl, cloransulam, cloransulam-methyl, closantel,clothianidin, clotrimazole, cloxyfonac, cloxyfonac-sodium, CMA,codlelure, colophonate, copper acetate, copper acetoarsenite, copperarsenate, copper carbonate, basic, copper hydroxide, copper naphthenate,copper oleate, copper oxychloride, copper silicate, copper sulfate,copper zinc chromate, coumachlor, coumafuryl, coumaphos, coumatetralyl,coumithoate, coumoxystrobin, CPMC, CPMF, CPPC, credazine, cresol,crimidine, crotamiton, crotoxyphos, crufomate, cryolite, cue-lure,cufraneb, cumyluron, cuprobam, cuprous oxide, curcumenol, cyanamide,cyanatryn, cyanazine, cyanofenphos, cyanophos, cyanthoate,cyantraniliprole, cyazofamid, cybutryne, cyclafuramid, cyclanilide,cyclethrin, cycloate, cycloheximide, cycloprate, cycloprothrin,cyclosulfamuron, cycloxaprid, cycloxydim, cycluron, cyenopyrafen,cyflufenamid, cyflumetofen, cyfluthrin, cyhalofop, cyhalofop-butyl,cyhalothrin, cyhexatin, cymiazole, cymiazole hydrochloride, cymoxanil,cyometrinil, cypendazole, cypermethrin, cyperquat, cyperquat chloride,cyphenothrin, cyprazine, cyprazole, cyproconazole, cyprodinil,cyprofuram, cypromid, cyprosulfamide, cyromazine, cythioate, daimuron,dalapon, dalapon-calcium, dalapon-magnesium, dalapon-sodium, daminozide,dayoutong, dazomet, dazomet-sodium, DB CP, d-camphor, DCIP, DCPTA, DDT,debacarb, decafentin, decarbofuran, dehydroacetic acid, delachlor,deltamethrin, demephion, demephion-O, demephion-S, demeton,demeton-methyl, demeton-O, demeton-O-methyl, demeton-S,demeton-S-methyl, demeton-S-methylsulphon, desmedipham, desmetryn,d-fanshiluquebingjuzhi, diafenthiuron, dialifos, di-allate, diamidafos,diatomaceous earth, diazinon, dibutyl phthalate, dibutyl succinate,dicamba, dicamba-diglycolamine, dicamba-dimethylammonium,dicamba-diolamine, dicamba-isopropylammonium, dicamba-methyl,dicamba-olamine, dicamba-potassium, dicamba-sodium, dicamba-trolamine,dicapthon, dichlobenil, dichlofenthion, dichlofluanid, dichlone,dichloralurea, dichlorbenzuron, dichlorflurenol, dichlorflurenol-methyl,dichlormate, dichlormid, dichlorophen, dichlorprop,dichlorprop-2-ethylhexyl, dichlorprop-butotyl,dichlorprop-dimethylammonium, dichlorprop-ethylammonium,dichlorprop-isoctyl, dichlorprop-methyl, dichlorprop-P,dichlorprop-P-2-ethylhexyl, dichlorprop-P-dimethylammonium,dichlorprop-potassium, dichlorprop-sodium, dichlorvos, dichlozoline,diclobutrazol, diclocymet, diclofop, diclofop-methyl, diclomezine,diclomezine-sodium, dicloran, diclosulam, dicofol, dicoumarol, dicresyl,dicrotophos, dicyclanil, dicyclonon, dieldrin, dienochlor, diethamquat,diethamquat dichloride, diethatyl, diethatyl-ethyl, diethofencarb,dietholate, diethyl pyrocarbonate, diethyltoluamide, difenacoum,difenoconazole, difenopenten, difenopenten-ethyl, difenoxuron,difenzoquat, difenzoquat metilsulfate, difethialone, diflovidazin,diflubenzuron, diflufenican, diflufenzopyr, diflufenzopyr-sodium,diflumetorim, dikegulac, dikegulac-sodium, dilor, dimatif, dimefluthrin,dimefox, dimefuron, dimepiperate, dimetachlone, dimetan, dimethacarb,dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimethipin,dimethirimol, dimethoate, dimethomorph, dimethrin, dimethyl carbate,dimethyl phthalate, dimethylvinphos, dimetilan, dimexano, dimidazon,dimoxystrobin, dinex, dinex-diclexine, dingjunezuo, diniconazole,diniconazole-M, dinitramine, dinobuton, dinocap, dinocap-4, dinocap-6,dinocton, dinofenate, dinopenton, dinoprop, dinosam, dinoseb, dinosebacetate, dinoseb-ammonium, dinoseb-diolamine, dinoseb-sodium,dinoseb-trolamine, dinosulfon, dinotefuran, dinoterb, dinoterb acetate,dinoterbon, diofenolan, dioxabenzofos, dioxacarb, dioxathion,diphacinone, diphacinone-sodium, diphenamid, diphenyl sulfone,diphenylamine, dipropalin, dipropetryn, dipyrithione, diquat, diquatdibromide, disparlure, disul, disulfuram, disulfoton, disul-sodium,ditalimfos, dithianon, dithicrofos, dithioether, dithiopyr, diuron,d-limonene, DMPA, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium,dodemorph, dodemorph acetate, dodemorph benzoate, dodicin, dodicinhydrochloride, dodicin-sodium, dodine, dofenapyn, dominicalure,doramectin, drazoxolon, DSMA, dufulin, EBEP, EBP, ecdysterone,edifenphos, eglinazine, eglinazine-ethyl, emamectin, emamectin benzoate,EMPC, empenthrin, endosulfan, endothal, endothal-diammonium,endothal-dipotassium, endothal-disodium, endothion, endrin,enestroburin, EPN, epocholeone, epofenonane, epoxiconazole,eprinomectin, epronaz, EPTC, erbon, ergocalciferol, erlujixiancaoan,esdépalléthrine, esfenvalerate, esprocarb, etacelasil, etaconazole,etaphos, etem, ethaboxam, ethachlor, ethalfluralin, ethametsulfuron,ethametsulfuron-methyl, ethaprochlor, ethephon, ethidimuron,ethiofencarb, ethiolate, ethion, ethiozin, ethiprole, ethirimol,ethoate-methyl, ethofumesate, ethohexadiol, ethoprophos, ethoxyfen,ethoxyfen-ethyl, ethoxyquin, ethoxysulfuron, ethychlozate, ethylformate, ethyl α-naphthaleneacetate, ethyl-DDD, ethylene, ethylenedibromide, ethylene dichloride, ethylene oxide, ethylicin, ethylmercury2,3-dihydroxypropyl mercaptide, ethylmercury acetate, ethylmercurybromide, ethylmercury chloride, ethylmercury phosphate, etinofen,etnipromid, etobenzanid, etofenprox, etoxazole, etridiazole, etrimfos,eugenol, EXD, famoxadone, famphur, fenamidone, fenaminosulf, fenamiphos,fenapanil, fenarimol, fenasulam, fenazaflor, fenazaquin, fenbuconazole,fenbutatin oxide, fenchlorazole, fenchlorazole-ethyl, fenchlorphos,fenclorim, fenethacarb, fenfluthrin, fenfuram, fenhexamid, fenitropan,fenitrothion, fenjuntong, fenobucarb, fenoprop, fenoprop-3-butoxypropyl,fenoprop-butomethyl, fenoprop-butotyl, fenoprop-butyl, fenoprop-isoctyl,fenoprop-methyl, fenoprop-potassium, fenothiocarb, fenoxacrim,fenoxanil, fenoxaprop, fenoxaprop-ethyl, fenoxaprop-P,fenoxaprop-P-ethyl, fenoxasulfone, fenoxycarb, fenpiclonil,fenpirithrin, fenpropathrin, fenpropidin, fenpropimorph, fenpyrazamine,fenpyroximate, fenridazon, fenridazon-potassium, fenridazon-propyl,fenson, fensulfothion, fenteracol, fenthiaprop, fenthiaprop-ethyl,fenthion, fenthion-ethyl, fentin, fentin acetate, fentin chloride,fentin hydroxide, fentrazamide, fentrifanil, fenuron, fenuron TCA,fenvalerate, ferbam, ferimzone, ferrous sulfate, fipronil, flamprop,flamprop-isopropyl, flamprop-M, flamprop-methyl, flamprop-M-isopropyl,flamprop-M-methyl, flazasulfuron, flocoumafen, flometoquin, flonicamid,florasulam, fluacrypyrim, fluazifop, fluazifop-butyl, fluazifop-methyl,fluazifop-P, fluazifop-P-butyl, fluazinam, fluazolate, fluazuron,flubendiamide, flubenzimine, flucarbazone, flucarbazone-sodium,flucetosulfuron, fluchloralin, flucofuron, flucycloxuron, flucythrinate,fludioxonil, fluenetil, fluensulfone, flufenacet, flufenerim,flufenican, flufenoxuron, flufenprox, flufenpyr, flufenpyr-ethyl,flufiprole, flumethrin, flumetover, flumetralin, flumetsulam, flumezin,flumiclorac, flumiclorac-pentyl, flumioxazin, flumipropyn, flumorph,fluometuron, fluopicolide, fluopyram, fluorbenside, fluoridamid,fluoroacetamide, fluorodifen, fluoroglycofen, fluoroglycofen-ethyl,fluoroimide, fluoromidine, fluoronitrofen, fluothiuron, fluotrimazole,fluoxastrobin, flupoxam, flupropacil, flupropadine, flupropanate,flupropanate-sodium, flupyradifurone, flupyrsulfuron,flupyrsulfuron-methyl, flupyrsulfuron-methyl-sodium, fluquinconazole,flurazole, flurenol, flurenol-butyl, flurenol-methyl, fluridone,fluorochloridone, fluoroxypyr, fluoroxypyr-butomethyl,fluoroxypyr-meptyl, flurprimidol, flursulamid, flurtamone, flusilazole,flusulfamide, fluthiacet, fluthiacet-methyl, flutianil, flutolanil,flutriafol, fluvalinate, fluxapyroxad, fluxofenim, folpet, fomesafen,fomesafen-sodium, fonofos, foramsulfuron, forchlorfenuron, formaldehyde,formetanate, formetanate hydrochloride, formothion, formparanate,formparanate hydrochloride, fosamine, fosamine-ammonium, fosetyl,fosetyl-aluminium, fosmethilan, fospirate, fosthiazate, fosthietan,frontalin, fuberidazole, fucaojing, fucaomi, funaihecaoling,fuphenthiourea, furalane, furalaxyl, furamethrin, furametpyr,furathiocarb, furcarbanil, furconazole, furconazole-cis, furethrin,furfural, furilazole, furmecyclox, furophanate, furyloxyfen,gamma-cyhalothrin, gamma-HCH, genit, gibberellic acid, gibberellins,gliftor, glufosinate, glufosinate-ammonium, glufosinate-P,glufosinate-P-ammonium, glufosinate-P-sodium, glyodin, glyoxime,glyphosate, glyphosate-diammonium, glyphosate-dimethylammonium,glyphosate-isopropylammonium, glyphosate-monoammonium,glyphosate-potassium, glyphosate-sesquisodium, glyphosate-trimesium,glyphosine, gossyplure, grandlure, griseofulvin, guazatine, guazatineacetates, halacrinate, halfenprox, halofenozide, halosafen,halosulfuron, halosulfuron-methyl, haloxydine, haloxyfop,haloxyfop-etotyl, haloxyfop-methyl, haloxyfop-P, haloxyfop-P-etotyl,haloxyfop-P-methyl, haloxyfop-sodium, HCH, hemel, hempa, HEOD,heptachlor, heptenophos, heptopargil, heterophos, hexachloroacetone,hexachlorobenzene, hexachlorobutadiene, hexachlorophene, hexaconazole,hexaflumuron, hexaflurate, hexylure, hexamide, hexazinone, hexylthiofos,hexythiazox, HHDN, holosulf, huancaiwo, huangcaoling, huanjunzuo,hydramethylnon, hydrargaphen, hydrated lime, hydrogen cyanide,hydroprene, hymexazol, hyquincarb, IAA, IBA, icaridin, imazalil,imazalil nitrate, imazalil sulfate, imazamethabenz,imazamethabenz-methyl, imazamox, imazamox-ammonium, imazapic,imazapic-ammonium, imazapyr, imazapyr-isopropylammonium, imazaquin,imazaquin-ammonium, imazaquin-methyl, imazaquin-sodium, imazethapyr,imazethapyr-ammonium, imazosulfuron, imibenconazole, imicyafos,imidacloprid, imidaclothiz, iminoctadine, iminoctadine triacetate,iminoctadine trialbesilate, imiprothrin, inabenfide, indanofan,indaziflam, indoxacarb, inezin, iodobonil, iodocarb, iodomethane,iodosulfuron, iodosulfuron-methyl, iodosulfuron-methyl-sodium,iofensulfuron, iofensulfuron-sodium, ioxynil, ioxynil octanoate,ioxynil-lithium, ioxynil-sodium, ipazine, ipconazole, ipfencarbazone,iprobenfos, iprodione, iprovalicarb, iprymidam, ipsdienol, ipsenol,IPSP, isamidofos, isazofos, isobenzan, isocarbamid, isocarbophos,isocil, isodrin, isofenphos, isofenphos-methyl, isolan, isomethiozin,isonoruron, isopolinate, isoprocarb, isopropalin, isoprothiolane,isoproturon, isopyrazam, isopyrimol, isothioate, isotianil, isouron,isovaledione, isoxaben, isoxachlortole, isoxadifen, isoxadifen-ethyl,isoxaflutole, isoxapyrifop, isoxathion, ivermectin, izopamfos,japonilure, japothrins, jasmolin I, jasmolin II, jasmonic acid,jiahuangchongzong, jiajizengxiaolin, jiaxiangjunzhi, jiecaowan,jiecaoxi, jodfenphos, juvenile hormone I, juvenile hormone II, juvenilehormone III, kadethrin, karbutilate, karetazan, karetazan-potassium,kasugamycin, kasugamycin hydrochloride, kejunlin, kelevan, ketospiradox,ketospiradox-potassium, kinetin, kinoprene, kresoxim-methyl, kuicaoxi,lactofen, lambda-cyhalothrin, latilure, lead arsenate, lenacil,lepimectin, leptophos, lindane, lineatin, linuron, lirimfos, litlure,looplure, lufenuron, lvdingjunzhi, lvxiancaolin, lythidathion, MAA,malathion, maleic hydrazide, malonoben, maltodextrin, MAMA, mancopper,mancozeb, mandipropamid, maneb, matrine, mazidox, MCPA,MCPA-2-ethylhexyl, MCPA-butotyl, MCPA-butyl, MCPA-dimethylammonium,MCPA-diolamine, MCPA-ethyl, MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl,MCPA-methyl, MCPA-olamine, MCPA-potassium, MCPA-sodium, MCPA-thioethyl,MCPA-trolamine, MCPB, MCPB-ethyl, MCPB-methyl, MCPB-sodium, mebenil,mecarbam, mecarbinzid, mecarphon, mecoprop, mecoprop-2-ethylhexyl,mecoprop-dimethylammonium, mecoprop-diolamine, mecoprop-ethadyl,mecoprop-isoctyl, mecoprop-methyl, mecoprop-P, mecoprop-P-2-ethylhexyl,mecoprop-P-dimethylammonium, mecoprop-P-isobutyl, mecoprop-potassium,mecoprop-P-potassium, mecoprop-sodium, mecoprop-trolamine, medimeform,medinoterb, medinoterb acetate, medlure, mefenacet, mefenpyr,mefenpyr-diethyl, mefluidide, mefluidide-diolamine,mefluidide-potassium, megatomoic acid, menazon, mepanipyrim,meperfluthrin, mephenate, mephosfolan, mepiquat, mepiquat chloride,mepiquat pentaborate, mepronil, meptyldinocap, mercuric chloride,mercuric oxide, mercurous chloride, merphos, mesoprazine, mesosulfuron,mesosulfuron-methyl, mesotrione, mesulfen, mesulfenfos, metaflumizone,metalaxyl, metalaxyl-M, metaldehyde, metam, metam-ammonium, metamifop,metamitron, metam-potassium, metam-sodium, metazachlor, metazosulfuron,metazoxolon, metconazole, metepa, metflurazon, methabenzthiazuron,methacrifos, methalpropalin, methamidophos, methasulfocarb, methazole,methfuroxam, methidathion, methiobencarb, methiocarb,methiopyrisulfuron, methiotepa, methiozolin, methiuron, methocrotophos,methometon, methomyl, methoprene, methoprotryne, methoquin-butyl,methothrin, methoxychlor, methoxyfenozide, methoxyphenone, methylapholate, methyl bromide, methyl eugenol, methyl iodide, methylisothiocyanate, methylacetophos, methylchloroform, methyldymron,methylene chloride, methylmercury benzoate, methylmercury dicyandiamide,methylmercury pentachlorophenoxide, methylneodecanamide, metiram,metobenzuron, metobromuron, metofluthrin, metolachlor, metolcarb,metominostrobin, metosulam, metoxadiazone, metoxuron, metrafenone,metribuzin, metsulfovax, metsulfuron, metsulfuron-methyl, mevinphos,mexacarbate, mieshuan, milbemectin, milbemycin oxime, milneb, mipafox,mirex, MNAF, moguchun, molinate, molosultap, monalide, monisouron,monochloroacetic acid, monocrotophos, monolinuron, monosulfuron,monosulfuron-ester, monuron, monuron TCA, morfamquat, morfamquatdichloride, moroxydine, moroxydine hydrochloride, morphothion, morzid,moxidectin, MSMA, muscalure, myclobutanil, myclozolin,N-(ethylmercury)-p-toluenesulphonanilide, nabam, naftalofos, naled,naphthalene, naphthaleneacetamide, naphthalic anhydride, naphthoxyaceticacids, naproanilide, napropamide, naptalam, naptalam-sodium, natamycin,neburon, niclosamide, niclosamide-olamine, nicosulfuron, nicotine,nifluridide, nipyraclofen, nitenpyram, nithiazine, nitralin, nitrapyrin,nitrilacarb, nitrofen, nitrofluorfen, nitrostyrene, nitrothal-isopropyl,norbormide, norflurazon, nomicotine, noruron, novaluron, noviflumuron,nuarimol, OCH, octachlorodipropyl ether, octhilinone, ofurace,omethoate, orbencarb, orfralure, ortho-dichlorobenzene, orthosulfamuron,oryctalure, orysastrobin, oryzalin, osthol, ostramone, oxabetrinil,oxadiargyl, oxadiazon, oxadixyl, oxamate, oxamyl, oxapyrazon,oxapyrazon-dimolamine, oxapyrazon-sodium, oxasulfuron, oxaziclomefone,oxine-copper, oxolinic acid, oxpoconazole, oxpoconazole fumarate,oxycarboxin, oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxyfluorfen,oxymatrine, oxytetracycline, oxytetracycline hydrochloride,paclobutrazol, paichongding, para-dichlorobenzene, parafluoron,paraquat, paraquat dichloride, paraquat dimetilsulfate, parathion,parathion-methyl, parinol, pebulate, pefurazoate, pelargonic acid,penconazole, pencycuron, pendimethalin, penflufen, penfluoron,penoxsulam, pentachlorophenol, pentanochlor, penthiopyrad, pentmethrin,pentoxazone, perfluidone, permethrin, pethoxamid, phenamacril, phenazineoxide, phenisopham, phenkapton, phenmedipham, phenmedipham-ethyl,phenobenzuron, phenothrin, phenproxide, phenthoate, phenylmercuriurea,phenylmercury acetate, phenylmercury chloride, phenylmercury derivativeof pyrocatechol, phenylmercury nitrate, phenylmercury salicylate,phorate, phosacetim, phosalone, phosdiphen, phosfolan, phosfolan-methyl,phosglycin, phosmet, phosnichlor, phosphamidon, phosphine, phosphocarb,phosphorus, phostin, phoxim, phoxim-methyl, phthalide, picloram,picloram-2-ethylhexyl, picloram-isoctyl, picloram-methyl,picloram-olamine, picloram-potassium, picloram-triethylammonium,picloram-tris(2-hydroxypropyl)ammonium, picolinafen, picoxystrobin,pindone, pindone-sodium, pinoxaden, piperalin, piperonyl butoxide,piperonyl cyclonene, piperophos, piproctanyl, piproctanyl bromide,piprotal, pirimetaphos, pirimicarb, pirimioxyphos, pirimiphos-ethyl,pirimiphos-methyl, plifenate, polycarbamate, polyoxins, polyoxorim,polyoxorim-zinc, polythialan, potassium arsenite, potassium azide,potassium cyanate, potassium gibberellate, potassium naphthenate,potassium polysulfide, potassium thiocyanate, potassiumα-naphthaleneacetate, pp′-DDT, prallethrin, precocene I, precocene II,precocene III, pretilachlor, primidophos, primisulfuron,primisulfuron-methyl, probenazole, prochloraz, prochloraz-manganese,proclonol, procyazine, procymidone, prodiamine, profenofos, profluazol,profluralin, profluthrin, profoxydim, proglinazine, proglinazine-ethyl,prohexadione, prohexadione-calcium, prohydrojasmon, promacyl, promecarb,prometon, prometryn, promurit, propachlor, propamidine, propamidinedihydrochloride, propamocarb, propamocarb hydrochloride, propanil,propaphos, propaquizafop, propargite, proparthrin, propazine,propetamphos, propham, propiconazole, propineb, propisochlor, propoxur,propoxycarbazone, propoxycarbazone-sodium, propyl isome,propyrisulfuron, propyzamide, proquinazid, prosuler, prosulfalin,prosulfocarb, prosulfuron, prothidathion, prothiocarb, prothiocarbhydrochloride, prothioconazole, prothiofos, prothoate, protrifenbute,proxan, proxan-sodium, prynachlor, pydanon, pymetrozine, pyracarbolid,pyraclofos, pyraclonil, pyraclostrobin, pyraflufen, pyraflufen-ethyl,pyrafluprole, pyramat, pyrametostrobin, pyraoxystrobin, pyrasulfotole,pyrazolynate, pyrazophos, pyrazosulfuron, pyrazosulfuron-ethyl,pyrazothion, pyrazoxyfen, pyresmethrin, pyrethrin I, pyrethrin II,pyrethrins, pyribambenz-isopropyl, pyribambenz-propyl, pyribencarb,pyribenzoxim, pyributicarb, pyriclor, pyridaben, pyridafol, pyridalyl,pyridaphenthion, pyridate, pyridinitril, pyrifenox, pyrifluquinazon,pyriftalid, pyrimethanil, pyrimidifen, pyriminobac, pyriminobac-methyl,pyrimisulfan, pyrimitate, pyrinuron, pyriofenone, pyriprole,pyripropanol, pyriproxyfen, pyrithiobac, pyrithiobac-sodium, pyrolan,pyroquilon, pyroxasulfone, pyroxsulam, pyroxychlor, pyroxyfur, quassia,quinacetol, quinacetol sulfate, quinalphos, quinalphos-methyl,quinazamid, quinclorac, quinconazole, quinmerac, quinoclamine,quinonamid, quinothion, quinoxyfen, quintiofos, quintozene, quizalofop,quizalofop-ethyl, quizalofop-P, quizalofop-P-ethyl,quizalofop-P-tefuryl, quwenzhi, quyingding, rabenzazole, rafoxanide,rebemide, resmethrin, rhodethanil, rhodojaponin-III, ribavirin,rimsulfuron, rotenone, ryania, saflufenacil, saijunmao, saisentong,salicylanilide, sanguinarine, santonin, schradan, scilliroside,sebuthylazine, secbumeton, sedaxane, selamectin, semiamitraz,semiamitraz chloride, sesamex, sesamolin, sethoxydim, shuangjiaancaolin,siduron, siglure, silafluofen, silatrane, silica gel, silthiofam,simazine, simeconazole, simeton, simetryn, sintofen, SMA, S-metolachlor,sodium arsenite, sodium azide, sodium chlorate, sodium fluoride, sodiumfluoroacetate, sodium hexafluorosilicate, sodium naphthenate, sodiumorthophenylphenoxide, sodium pentachlorophenoxide, sodium polysulfide,sodium thiocyanate, sodium α-naphthaleneacetate, sophamide, spinetoram,spinosad, spirodiclofen, spiromesifen, spirotetramat, spiroxamine,streptomycin, streptomycin sesquisulfate, strychnine, sulcatol,sulcofuron, sulcofuron-sodium, sulcotrione, sulfallate, sulfentrazone,sulfuram, sulfluramid, sulfometuron, sulfometuron-methyl, sulfosulfuron,sulfotep, sulfoxaflor, sulfoxide, sulfoxime, sulfur, sulfuric acid,sulfuryl fluoride, sulglycapin, sulprofos, sultropen, swep,tau-fluvalinate, tavron, tazimcarb, TCA, TCA-ammonium, TCA-calcium,TCA-ethadyl, TCA-magnesium, TCA-sodium, TDE, tebuconazole, tebufenozide,tebufenpyrad, tebufloquin, tebupirimfos, tebutam, tebuthiuron,tecloftalam, tecnazene, tecoram, teflubenzuron, tefluthrin,tefuryltrione, tembotrione, temephos, tepa, TEPP, tepraloxydim,terallethrin, terbacil, terbucarb, terbuchlor, terbufos, terbumeton,terbuthylazine, terbutryn, tetcyclacis, tetrachloroethane,tetrachlorvinphos, tetraconazole, tetradifon, tetrafluoron,tetramethrin, tetramethylfluthrin, tetramine, tetranactin, tetrasul,thallium sulfate, thenylchlor, theta-cypermethrin, thiabendazole,thiacloprid, thiadifluor, thiamethoxam, thiapronil, thiazafluoron,thiazopyr, thicrofos, thicyofen, thidiazimin, thidiazuron,thiencarbazone, thiencarbazone-methyl, thifensulfuron,thifensulfuron-methyl, thifluzamide, thiobencarb, thiocarboxime,thiochlorfenphim, thiocyclam, thiocyclam hydrochloride, thiocyclamoxalate, thiodiazole-copper, thiodicarb, thiofanox, thiofluoximate,thiohempa, thiomersal, thiometon, thionazin, thiophanate,thiophanate-methyl, thioquinox, thiosemicarbazide, thiosultap,thiosultap-diammonium, thiosultap-disodium, thiosultap-monosodium,thiotepa, thiram, thuringiensin, tiadinil, tiaojiean, tiocarbazil,tioclorim, tioxymid, tirpate, tolclofos-methyl, tolfenpyrad,tolylfluanid, tolylmercury acetate, topramezone, tralkoxydim,tralocythrin, tralomethrin, tralopyril, transfluthrin, transpermethrin,tretamine, triacontanol, triadimefon, triadimenol, triafamone,tri-allate, triamiphos, triapenthenol, triarathene, triarimol,triasulfuron, triazamate, triazbutil, triaziflam, triazophos,triazoxide, tribenuron, tribenuron-methyl, tribufos, tributyltin oxide,tricamba, trichlamide, trichlorfon, trichlormetaphos-3, trichloronat,triclopyr, triclopyr-butotyl, triclopyr-ethyl,triclopyr-triethylammonium, tricyclazole, tridemorph, tridiphane,trietazine, trifenmorph, trifenofos, trifloxystrobin, trifloxysulfuron,trifloxysulfuron-sodium, triflumizole, triflumuron, trifluralin,triflusulfuron, triflusulfuron-methyl, trifop, trifop-methyl,trifopsime, triforine, trihydroxytriazine, trimedlure, trimethacarb,trimeturon, trinexapac, trinexapac-ethyl, triprene, tripropindan,triptolide, tritac, triticonazole, tritosulfuron, trunc-call,uniconazole, uniconazole-P, urbacide, uredepa, valerate, validamycin,valifenalate, valone, vamidothion, vangard, vaniliprole, vernolate,vinclozolin, warfarin, warfarin-potassium, warfarin-sodium,xiaochongliulin, xinjunan, xiwojunan, XMC, xylachlor, xylenols,xylylcarb, yishijing, zarilamid, zeatin, zengxiaoan, zeta-cypermethrin,zinc naphthenate, zinc phosphide, zinc thiazole, zineb, ziram,zolaprofos, zoxamide, zuomihuanglong, α-chlorohydrin, α-ecdysone,α-multistriatin, and α-naphthaleneacetic acid.
 4. A compositionaccording to claim 1 further comprising an agriculturally acceptablecarrier.
 5. A composition according to claim 1 wherein said molecule isin the form of a pesticidally acceptable acid addition salt.
 6. Acomposition according to claim 1 wherein said molecule is in the form ofa salt derivative.
 7. A composition according to claim 1 wherein saidmolecule is in the form a hydrate.
 8. A composition according to claim 1wherein said molecule is in the form an ester derivative.
 9. Acomposition according to claim 1 wherein said molecule is in the form acrystal polymorph.
 10. A composition according to claim 1 wherein saidmolecule has a ²H in place of ¹H.
 11. A composition according to claim 1wherein said molecule has a ¹⁴C in place of a ¹²C.
 12. A compositionaccording to claim 1 further comprising a biopesticide.
 13. Acomposition according to claim 1 further comprising one or more of thefollowing compounds: (a)3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one;(b)3-(4′-chloro-2,4-dimethyl[1,1′-biphenyl]-3-yl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one;(c) 4-[[(6-chloro-3-pyridinyl)methyl]methylamino]-2(5H)-furanone; (d)4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5H)-furanone; (e)3-chloro-N2-[(1S)-1-methyl-2-(methylsulfonyl)ethyl]-N1-[2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]-1,2-benzenedicarboxamide;(f) 2-cyano-N-ethyl-4-fluoro-3-methoxy-benenesulfonamide; (g)2-cyano-N-ethyl-3-methoxy-benzenesulfonamide; (h)2-cyano-3-difluoromethoxy-N-ethyl-4-fluoro-benzenesulfonamide; (i)2-cyano-3-fluoromethoxy-N-ethyl-benzenesulfonamide; (j)2-cyano-6-fluoro-3-methoxy-N,N-dimethyl-benzenesulfonamide; (k)2-cyano-N-ethyl-6-fluoro-3-methoxy-N-methyl-benzenesulfonamide; (l)2-cyano-3-difluoromethoxy-N,N-dimethylbenzenesulfon-amide; (m)3-(difluoromethyl)-N-[2-(3,3-dimethylbutyl)phenyl]-1-methyl-1H-pyrazole-4-carboxamide;(n)N-ethyl-2,2-dimethylpropionamide-2-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)hydrazone; (O)N-ethyl-2,2-dichloro-1-methylcyclopropane-carboxamide-2-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)hydrazone nicotine; (p)O-{(E-)-[2-(4-chloro-phenyl)-2-cyano-1-(2-trifluoromethylphenyl)-vinyl]}S-methylthiocarbonate; (q)(E)-N-1-[(2-chloro-1,3-thiazol-5-ylmethyl)]-N2-cyano-N1-methylacetamidine;(r)1-(6-chloropyridin-3-ylmethyl)-7-methyl-8-nitro-1,2,3,5,6,7-hexahydro-imidazo[1,2-a]pyridin-5-ol;(s) 4-[4-chlorophenyl-(2-butylidine-hydrazono)methyl)]phenyl mesylate;and (t)N-Ethyl-2,2-dichloro-1-methylcyclopropanecarboxamide-2-(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyl)hydrazone.14. A composition according to claim 1 further comprising a compoundhaving one or more of the following modes of action:acetylcholinesterase inhibitor; sodium channel modulator; chitinbiosynthesis inhibitor; GABA and glutamate-gated chloride channelantagonist; GABA and glutamate-gated chloride channel agonist;acetylcholine receptor agonist; acetylcholine receptor antagonist; MET Iinhibitor; Mg-stimulated ATPase inhibitor; nicotinic acetylcholinereceptor; Midgut membrane disrupter; oxidative phosphorylationdisrupter, and ryanodine receptor (RyRs).
 15. A composition according toclaim 1 further comprising a seed.
 16. A composition according to claim1 further comprising a seed that has been genetically modified toexpress one or more specialized traits.
 17. A composition according toclaim 1 wherein said composition is encapsulated inside, or placed onthe surface of, a capsule.
 18. A composition according to claim 1wherein said composition is encapsulated inside, or placed on thesurface of, a capsule, wherein said capsule has a diameter of about100-900 nanometers or about 10-900 microns.
 19. A process comprisingapplying a composition according to claim 1, to an area to control apest, in an amount sufficient to control such pest.
 20. A processaccording to claim 19 wherein said pest is selected from beetles,earwigs, cockroaches, flies, aphids, scales, whiteflies, leafhoppers,ants, wasps, termites, moths, butterflies, lice, grasshoppers, locusts,crickets, fleas, thrips, bristletails, mites, ticks, nematodes, andsymphylans.
 21. A process according to claim 19 wherein said pest isfrom the Phyla Nematoda or Arthropoda.
 22. A process according to claim19 wherein said pest is from the Subphyla Chelicerata, Myriapoda, orHexapoda.
 23. A process according to claim 19 wherein said pest is fromthe Class of Arachnida, Symphyla, or Insecta.
 24. A process according toclaim 19 wherein said pest is from the Order Anoplura, Order Coleoptera,Order Dermaptera, Order Blattaria, Order Diptera, Order Hemiptera, OrderHymenoptera, Order Isoptera, Order Lepidoptera, Order Mallophaga, OrderOrthoptera, Order Siphonaptera, Order Thysanoptera, Order Thysanura,Order Acarina, or Order Symphyla.
 25. A process according to claim 19wherein said pest is BAW, CEW, or GPA.
 26. A process according to claim19 wherein said amount is from about 0.01 grams per hectare to about5000 grams per hectare.
 27. A process according to claim 19 wherein saidamount is from about 0.1 grams per hectare to about 500 grams perhectare.
 28. A process according to claim 19 wherein said amount is fromabout 1 gram per hectare to about 50 grams per hectare.
 29. A processaccording to claim 19 wherein said area is an area where apples, corn,cotton, soybeans, canola, wheat, rice, sorghum, barley, oats, potatoes,oranges, alfalfa, lettuce, strawberries, tomatoes, peppers, crucifers,pears, tobacco, almonds, sugar beets, or beans, are growing, or theseeds thereof are going to be planted.
 30. A process according to claim19 further comprising applying said composition to a geneticallymodified plant that has been genetically modified to express one or morespecialized traits.
 31. A process according to claim 1 where saidcomposition further comprise ammonium sulfate.
 32. A process comprising:orally administering; or topically applying; a composition according toclaim 1, to a non-human animal, to control endoparasites, ectoparasites,or both.
 33. A process comprising applying a composition according toclaim 1 to a plant to enhance the plant's health, yield, vigor, quality,or tolerance, at a time when pest activity is low.